Browsing by Subject "TRANSLOCATION"

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  • Haider, Zahra; Larsson, Pär; Landfors, Mattias; Köhn, Linda; Schmiegelow, Kjeld; Flægstad, Trond; Kanerva, Jukka; Heyman, Mats; Hultdin, Magnus; Degerman, Sofie (2019)
    Classification of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T-ALL patients were characterized by genome-wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P <0.001) and mitotic age (P <0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2-1, and novel genes in T-ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP- subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL-TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP-), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T-ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies.
  • Allolio, Christoph; Magarkar, Aniket; Jurkiewicz, Piotr; Baxova, Katarina; Javanainen, Matti; Mason, Philip E.; Sachl, Radek; Cebecauer, Marek; Hof, Martin; Horinek, Dominik; Heinz, Veronika; Rachel, Reinhard; Ziegler, Christine M.; Schröfel, Adam; Jungwirth, Pavel (2018)
    Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cell-penetrating peptide-nonaarginine-are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.
  • de Luca, Sergio; Seal, Prasenjit; Parekh, Harendra S.; Tupally, Karnaker R.; Smith, Sean C. (2020)
    The mechanism by which cell-penetrating peptides and antimicrobial peptides cross plasma membranes is unknown, as is how cell-penetrating peptides facilitate drug delivery, mediating the transport of small molecules. Once nondisruptive and nonendocytotic pathways are excluded, pore formation is one of the proposed mechanisms, including toroidal, barrel-stave, or carpet models. Spontaneous pores are observed in coarse-grained simulations and less often in molecular dynamics simulations. While pores are widely assumed and inferred, there is no unambiguous experimental evidence of the existence of pores. Some recent experimental studies contradict the mechanistic picture of pore formation, however, highlighting the possibility of a direct translocation pathway that is both nondisruptive and nonendocytotic. In this work, a model is proposed a model for peptide (linear and dendritic) translocation which does not require the presence of pores and which potentially accords with such experiments. It is suggested that a charged peptide, as it experiences an increasingly hydrophobic environment within the membrane surface, can utilize a proton chain transfer mechanism to shed its protons to counter ions or potentially phospholipid head groups in the membrane skin region, thereby becoming compatible with the hydrophobic interior of the membrane. This increases the likelihood to move into the highly hydrophobic core of the membrane and ultimately reach the opposite leaflet to re-acquire protons again, suggesting a potential "chameleon" mechanism for non-disruptive and non-endocytotic membrane translocation. The molecular dynamics simulations reveal stability of peptide bridges joining two membrane leaflets and demonstrate that this can facilitate cross-membrane transport of small drug molecules.
  • Ikonen, Elina; Zhou, Xin (2021)
    Cholesterol represents the most abundant single lipid in mammalian cells. How its asymmetric distribution between subcellular membranes is achieved and maintained attracts considerable interest. One of the challenges is that cholesterol rarely is transported alone, but rather is coupled with heterotypic transport and metabolism of other lipids, in particular phosphoinositides, phosphatidylserine, and sphingolipids. This perspective summarizes the major exo- and endocytic cholesterol transport routes and how lipid transfer proteins at membrane contacts and membrane transport intersect along these routes. It discusses the cotransport of cholesterol with other lipids in mammalian cells and reviews emerging evidence related to the physiological relevance of this process.
  • Tranter, Dale; Paatero, Anja O.; Kawaguchi, Shinsaku; Kazemi, Soheila; Serrill, Jeffrey D.; Kellosalo, Juho; Vogel, Walter K.; Richter, Uwe; Mattos, Daphne R.; Wan, Xuemei; Thornburg, Christopher C.; Oishi, Shinya; McPhail, Kerry L.; Ishmael, Jane E.; Paavilainen, Ville O. (2020)
    Coibamide A (CbA) is a marine natural product with potent antiproliferative activity against human cancer cells and a unique selectivity profile. Despite promising antitumor activity, the mechanism of cytotoxicity and specific cellular target of CbA remain unknown. Here, we develop an optimized synthetic CbA photoaffinity probe (photo-CbA) and use it to demonstrate that CbA directly targets the Sec61 alpha subunit of the Sec61 protein translocon. CbA binding to Sec61 results in broad substratenonselective inhibition of ER protein import and potent cytotoxicity against specific cancer cell lines. CbA targets a lumenal cavity of Sec61 that is partially shared with known Sec61 inhibitors, yet profiling against resistance conferring Sec61 alpha mutations identified from human HCT116 cells su ests a distinct binding mode for CbA. Specifically, despite conferring strong resistance to all previously known Sec61 inhibitors, the Sec61 alpha mutant R66I remains sensitive to CbA. A further unbiased screen for Sec61 alpha resistance mutations identified the CbA-resistant mutation S71P, which confirms nonidentical binding sites for CbA and apratoxin A and supports the susceptibility of the Sec61 plug region for channel inhibition. Remarkably, CbA, apratoxin A, and ipomoeassin F do not display comparable patterns of potency and selectivity in the NCI60 panel of human cancer cell lines. Our work connecting CbA activity with selective prevention of secretory and membrane protein biogenesis by inhibition of Sec61 opens up possibilities for developing new Sec61 inhibitors with improved druglike properties that are based on the coibamide pharmacophore.
  • Gorbikova, Elena; Kalendar, Ruslan (2020)
    Cytochrome c oxidase is terminal enzyme in the respiratory chain of mitochondria and many aerobic bacteria. It catalyzes reduction of oxygen to water. During its catalysis, CcO proceeds through several quite stable intermediates (R, A, PR/M, O/OH, E/EH). This work is concentrated on the elucidation of the differences between structures of oxidized intermediates O and OH in different CcO variants and at different pH values. Oxidized intermediates of wild type and mutated CcO from Paracoccus denitrificans were studied by means of static and time-resolved Fourier-transform infrared spectroscopy in acidic and alkaline conditions in the infrared region 1800–1000 cm−1. No reasonable differences were found between all variants in these conditions, and in this spectral region. This finding means that the binuclear center of oxygen reduction keeps a very similar structure and holds the same ligands in the studied conditions. The further investigation in search of differences should be performed in the 4000–2000 cm−1 IR region where water ligands absorb.
  • Skok, Žiga; Barančoková, Michaela; Benek, Ondřej; Cruz, Cristina Durante; Tammela, Päivi; Tomašič, Tihomir; Zidar, Nace; Mašič, Lucija Peterlin; Zega, Anamarija; Stevenson, Clare E. M.; Mundy, Julia E. A.; Lawson, David M.; Maxwell, Anthony; Kikelj, Danijel; Ilaš, Janez (2020)
    We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC50 = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 mu M), and efflux impaired E. coli strain (MIC = 0.78 mu M), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.
  • Morimoto, Nobuyuki; Takei, Riho; Wakamura, Masaru; Oishi, Yoshifumi; Nakayama, Masafumi; Suzuki, Makoto; Yamamoto, Masaya; Winnik, Francoise M. (2018)
    Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 <M-n <74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (alpha or omega). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M-n <30.0 kg/mol, lightly grafted with PEG chains (<5 mol %) labeled with Rho in the omega-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.
  • Keinanen, Outi; Dayts, Eric J.; Rodriguez, Cindy; Sarrett, Samantha M.; Brennan, James M.; Sarparanta, Mirkka; Zeglis, Brian M (2021)
    The proliferation of plastics in the environment continues at an alarming rate. Plastic particles have been found to be persistent and ubiquitous pollutants in a variety of environments, including sea water, fresh water, soil, and air. In light of this phenomenon, the scientific and medical communities have become increasingly wary of the dangers posed to human health by chronic exposure to microplastics (
  • Ran, Li; Wan, Xing; Takala, Timo; Saris, Per (2021)
    The yeastSaccharomyces boulardiiis well known for its probiotic effects such as treating or preventing gastrointestinal diseases. Due to its ability to survive in stomach and intestine,S. boulardiicould be applied as a vehicle for producing and delivering bioactive substances of interest to human gut. In this study, we cloned the genelecCencoding the antilisterial peptide leucocin C from lactic acid bacteriumLeuconostoc carnosuminS. boulardii. The constructedS. boulardiistrain secreted a peptide, which had molecular weight corresponding to leucocin C in SDS-PAGE. The peptide band inhibitedListeria monocytogenesin gel overlay assay. Likewise, concentratedS. boulardiiculture supernatant inhibited the growth ofL. monocytogenes. The growth profile and acid tolerance of the leucocin C secretingS. boulardiiwere similar as those of the strain carrying the empty vector. We further demonstrated that the cells of the leucocin C producingS. boulardiiefficiently killedL. monocytogenes, also without antibiotic selection pressure. These results showed that antilisterial activity could be added to the arsenal of probiotic activities ofS. boulardii, demonstrating its potential as a carrier for therapeutics delivery.
  • Alves, Ana Catarina; Magarkar, Aniket; Horta, Miguel; Lima, Jose L. F. C.; Bunker, Alex; Nunes, Claudia; Reis, Salette (2017)
    Despite doxorubicin being commonly used in chemotherapy there still remain significant holes in our knowledge regarding its delivery efficacy and an observed resistance mechanism that is postulated to involve the cell membrane. One possible mechanism is the efflux by protein P-gp, which is found predominantly in cholesterol enriched domains. Thereby, a hypothesis for the vulnerability of doxorubicin to efflux through P-gp is its enhanced affinity for the ordered cholesterol rich regions of the plasma membrane. Thus, we have studied doxorubicin's interaction with model membranes in a cholesterol rich, ordered environment and in liquid-disordered cholesterol poor environment. We have combined three separate experimental protocols: UV-Vis spectrophotometry, fluorescence quenching and steady-state anisotropy and computational molecular dynamics modeling. Our results show that the presence of cholesterol induces a change in membrane structure and doesn't impair doxorubicin's membrane partitioning, but reduces drug's influence on membrane fluidity without directly interacting with it. It is thus possible that the resistance mechanism that lowers the efficacy of doxorubicin, results from an increased density in membrane regions where the efflux proteins are present. This work represents a successful approach, combining experimental and computational studies of membrane based systems to unveil the behavior of drugs and candidate drug molecules.
  • Wang, Jun; Conti, David; Epeldegui, Marta; Ollikainen, Miina; Tyndale, Rachel F.; Hwang, Amie Eunah; Magpantay, Larry; Mack, Thomas McCulloch; Martinez-Maza, Otoniel; Kaprio, Jaakko; Cozen, Wendy (2021)
    Simple Summary: Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To help understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. We validated self-reported smoking history by measuring serum cotinine, a metabolite of nicotine, from previously collected frozen serum samples. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). We found that four immune response biomarkers were higher and one was lower among smoking compared to non-smoking twins. The strongest association was observed for CCL17/TARC, a biomarker elevated in Hodgkin lymphoma patients. Immune biomarker levels were similar in former smokers and non-smokers. Current smoking may increase levels of immune proteins that could partially explain the association between smoking and risk of certain lymphomas.Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of > 3.08 ng/mL and & LE;3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (P-trend < 0.05). The strongest association was observed for CCL17/TARC (P-trend = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas.
  • Li, Kun-Mou; Wilkinson, Craig; Kellosalo, Juho; Tsai, Jia-Yin; Kajander, Tommi; Jeuken, Lars J. C.; Sun, Yuh-Ju; Goldman, Adrian (2016)
    Membrane-bound pyrophosphatases (M-PPases), which couple proton/sodium ion transport to pyrophosphate synthesis/hydrolysis, are important in abiotic stress resistance and in the infectivity of protozoan parasites. Here, three M-PPase structures in different catalytic states show that closure of the substrate-binding pocket by helices 5-6 affects helix 13 in the dimer interface and causes helix 12 to move down. This springs a 'molecular mousetrap', repositioning a conserved aspartate and activating the nucleophilic water. Corkscrew motion at helices 6 and 16 rearranges the key ionic gate residues and leads to ion pumping. The pumped ion is above the ion gate in one of the ion-bound structures, but below it in the other. Electrometric measurements show a single-turnover event with a non-hydrolysable inhibitor, supporting our model that ion pumping precedes hydrolysis. We propose a complete catalytic cycle for both proton and sodium-pumping M-PPases, and one that also explains the basis for ion specificity.
  • Naakka, Erika; Barros-Filho, Mateus Camargo; Adnan-Awad, Shady; Al-Samadi, Ahmed; Marchi, Fábio Albuquerque; Kuasne, Hellen; Korelin, Katja; Suleymanova, Ilida; Brown, Amy Louise; Scapulatempo-Neto, Cristovam; Lourenço, Silvia Vanessa; Castilho, Rogério Moraes; Kowalski, Luiz Paulo; Mäkitie, Antti; Araújo, Vera Cavalcanti; Leivo, Ilmo; Rogatto, Silvia Regina; Salo, Tuula; Passador-Santos, Fabricio (2022)
    Objectives: To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers. Material and Methods: Gene and miRNA expression arrays were performed in 35 MECs and six NSGs. Results: We found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT. Conclusion: The in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.
  • Ranki, Annamari; Vakeva, Liisa; Sipila, Laura; Krohn, Kai (2011)
  • Djurabekova, Amina; Haapanen, Outi; Sharma, Vivek (2020)
    In the aerobic respiratory chains of many organisms, complex I functions as the first electron input. By reducing ubiquinone (Q) to ubiquinol, it catalyzes the translocation of protons across the membrane as far as ~200 Å from the site of redox reactions. Despite significant amount of structural and biochemical data, the details of redox coupled proton pumping in complex I are poorly understood. In particular, the proton transfer pathways are extremely difficult to characterize with the current structural and biochemical techniques. Here, we applied multiscale computational approaches to identify the proton transfer paths in the terminal antiporter-like subunit of complex I. Data from combined classical and quantum chemical simulations reveal for the first time structural elements that are exclusive to the subunit, and enables the enzyme to achieve coupling between the spatially separated Q redox reactions and proton pumping. By studying long time scale protonation and hydration dependent conformational dynamics of key amino acid residues, we provide novel insights into the proton pumping mechanism of complex I.
  • Wikström, Mårten; Sharma, Vivek (2018)
    Abstract Cytochrome c oxidase is a remarkable energy transducer that seems to work almost purely by Coulombic principles without the need for significant protein conformational changes. In recent years it has become possible to follow key partial reactions of the catalytic cycle in real time, both with respect to electron and proton movements. These experiments have largely set the stage for the proton pump mechanism. The structures of the catalytic binuclear heme‑copper site that is common to the huge family of heme‑copper oxidases, are today well understood throughout the catalytic cycle of oxygen reduction to water based on both spectroscopic studies and quantum chemical calculations. Here, we briefly review this progress, and add some recent details into how the proton pump mechanism is protected from failure by leakage.
  • Nagy, Szabolcs; Polgar, Peter J.; Andersson, Magnus; Kovacs, Andras (2016)
    The aim of the present study was to test the FXCycle PI/RNase kit for routine DNA analyses in order to detect breeding bulls and/or insemination doses carrying cytogenetic aberrations. In a series of experiments we first established basic DNA histogram parameters of cytogenetically healthy breeding bulls by measuring the intraspecific genome size variation of three animals, then we compared the histogram profiles of bulls carrying cytogenetic defects to the baseline values. With the exception of one case the test was able to identify bulls with cytogenetic defects. Therefore, we conclude that the assay could be incorporated into the laboratory routine where flow cytometry is applied for semen quality control.
  • Kiessling, Andreas R.; Malik, Anchal; Goldman, Adrian (2020)
    Adhesion is the initial step in the infection process of gram-negative bacteria. It is usually followed by the formation of biofilms that serve as a hub for further spread of the infection. Type V secretion systems engage in this process by binding to components of the extracellular matrix, which is the first step in the infection process. At the same time they provide protection from the immune system by either binding components of the innate immune system or by establishing a physical layer against aggressors. Trimeric autotransporter adhesins (TAAs) are of particular interest in this family of proteins as they possess a unique structural composition which arises from constraints during translocation. The sequence of individual domains can vary dramatically while the overall structure can be very similar to one another. This patchwork approach allows researchers to draw conclusions of the underlying function of a specific domain in a structure-based approach which underscores the importance of solving structures of yet uncharacterized TAAs and their individual domains to estimate the full extent of functions of the protein a priori. Here, we describe recent advances in understanding the translocation process of TAAs and give an overview of structural motifs that are unique to this class of proteins. The role of BpaC in the infection process of Burkholderia pseudomallei is highlighted as an exceptional example of a TAA being at the centre of infection initiation.
  • Storvall, Sara; Leijon, Helena; Ryhänen, Eeva; Louhimo, Johanna; Haglund, Caj; Schalin-Jäntti, Camilla; Arola, Johanna (2019)
    Introduction: Parathyroid carcinoma represents a rare cause of primary hyperparathyroidism. Distinguishing carcinoma from the benign tumors underlying primary hyperparathyroidism remains challenging. The diagnostic criteria for parathyroid carcinoma are local and/or metastatic spreading. Atypical parathyroid adenomas share other histological features with carcinomas but lack invasive growth. Somatostatin receptors are commonly expressed in different neuro endocrine tumors, but whether this also holds for parathyroid tumors remains unknown. Aim: Our aim is to examine the immunohistochemical expression of somatostatin receptor 1-5 in parathyroid typical adenomas, atypical adenomas and carcinomas. Methods: We used a tissue microarray construct from a nationwide cohort of parathyroid carcinomas (n = 32), age- and gender-matched typical parathyroid adenomas (n = 72) and atypical parathyroid adenomas (n = 27) for immunohistochemistry of somatostatin receptor subtypes 1-5. We separately assessed cytoplasmic, membrane and nuclear expression and also investigated the associations with histological, biochemical and clinical characteristics. Results: All parathyroid tumor subgroups expressed somatostatin receptors, although membrane expression appeared negligible. Except for somatostatin receptor 1, expression patterns differed between the three tumor types. Adenomas exhibited the weakest and carcinomas the strongest expression of somatostatin receptor 2, 3, 4 and 5. We observed the largest difference for cytoplasmic somatostatin receptor 5 expression. Conclusions: Parathyroid adenomas, atypical adenomas and carcinomas all express somatostatin receptor subtypes 1-5. Somatostatin receptor 5 may serve as a potential tumor marker for malignancy. Studies exploring the role of somatostatin receptor imaging and receptor-specific therapies in patients with parathyroid car cinomas are needed.