title: Pin1 expression contributes to lung cancer: Prognosis and carcinogenesis.
abstract: Lung cancer remains the most common cause of death for malignancy in both men and women. Current therapies for NSCLC patients are inefficient due to the lack of diagnostic and therapeutic markers. The phospho-Ser/Thr-Pro specific prolyl-isomerase Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a target for cancer therapy. We identified 79 cases with the follow-up survival and investigated the clinical relevance of Pin1 expression in NSCLC patients. To validate the oncogenic potential of Pin1 in lung cells, we overexpressed Pin1 in Glc82 cells, and downregulated Pin1 by RNA interference in H1299 cells. The 5-year survival rate of the 79 patients was 54.6%. High expression of Pin1 correlated with poor survival by univariate analysis as well as by multivariate analysis, demonstrating that high expression of Pin1 was an independent prognostic factor. Consistent with the clinical findings, overexpression of Pin1 in Glc82 cells increased cell growth and colony formation and tumorigenicity in nude mice including cell migration, invasion. To further validate the role of Pin1 in lung cancer carcinogenesis, lentivirus-mediated siRNA targeting of Pin1 resulted in the stable suppression of both cell growth, anchorage-independent growth in soft agar and tumorigenic including cell migration, invasion in H1299 cells. Pin1 expression may be an unfavorable prognostic factor in patients of NSCLC patients, and these results indicate that Pin1 may have a role in tumor development and metastasis and thus could serve as a novel target for treatment of NSCLC.
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College, Beijing, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Tan
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Junting
authors.initials: J
authors.lastname: Wan
authors.forename: Jie
authors.initials: J
authors.lastname: Hang
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Chen
authors.forename: Baozhong
authors.initials: B
authors.lastname: Li
authors.forename: Cuiyan
authors.initials: C
authors.lastname: Zhang
authors.forename: Kang
authors.initials: K
authors.lastname: Shao
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Susheng
authors.initials: S
authors.lastname: Shi
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Feng
authors.forename: Ning
authors.initials: N
authors.lastname: Lv
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhao
authors.forename: Dapeng
authors.initials: D
authors.lastname: Ding
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Meihua
authors.initials: M
authors.lastname: Xiong
authors.forename: Jie
authors.initials: J
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D019696:Peptidylprolyl Isomerase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D016019:Survival Analysis; D014410:Tumor Stem Cell Assay
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse