title: Tumor suppressive activity of prolyl isomerase Pin1 in renal cell carcinoma.
abstract: Pin1 specifically recognizes and catalyzes the cis-trans isomerization of phosphorylated-Ser/Thr-Pro bonds, which modulate the stability, localization, and function of numerous Pin1 targets involved in tumor progression. However, the role of Pin1 in cancer remains enigmatic as the gene is located on chromosome 19p13.2, which is a region subject to loss of heterozygosity in several tumors. Since Pin1 protein is frequently under-expressed in kidney cancer, we have explored its role in human clear cell renal cell carcinoma (ccRCC). Here we show evidence for PIN1 gene deletion and mRNA under-expression as a mechanism of Pin1 reduction in ccRCC tumors. We demonstrate that restoration of Pin1 in cell lines found to be deficient in Pin1 protein expression can attenuate the growth of ccRCC cells in soft agar and a xenograft tumor model. Moreover, this ability of Pin1 to negatively influence tumor growth in ccRCC cells may be dependent on the presence of functional p53, which is infrequently mutated in ccRCC. These observations suggest Pin1 may have a mild tumor suppressive role in ccRCC.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Teng
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hacker
authors.forename: Shufen
authors.initials: S
authors.lastname: Chen
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Means
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016159:Tumor Suppressor Protein p53; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse