title: PC-1/PrLZ contributes to malignant progression in prostate cancer.
abstract: PC-1/PrLZ gene overexpression has been identified to be associated with prostate cancer progression. Previous studies have revealed that PC-1 possesses transforming activity and confers malignant phenotypes to mouse NIH3T3 cells. However, the functional relevance of PC-1 expression changes during prostate cancer development and progression remains to be evaluated. In this study, gain-of-function and loss-of-function analyses in LNCaP and C4-2 cells, respectively, were implemented. Experimental data showed that PC-1 expression was in positive correlation with prostate cancer cell growth and anchor-independent colony formation in vitro, as well as tumorigenicity in athymic BALB/c mice. Moreover, PC-1 expression was also found to promote androgen-independent progression and androgen antagonist Casodex resistance in prostate cancer cells. These results indicate that PC-1 contributes to androgen-independent progression and malignant phenotypes in prostate cancer cells. Furthermore, molecular evidence revealed that PC-1 expression stimulated Akt/protein kinase B signaling pathway, which has been implicated to play important roles in promoting androgen refractory progression in prostate cancer. Increased PC-1 levels in C4-2 cells may represent an adaptive response in prostate cancer, mediating androgen-independent growth and malignant progression. Inhibiting PC-1 expression may represent a novel therapeutic strategy to delay prostate cancer progression.
authors: Laboratory of Molecular Oncology, Institute of Biotechnology, Beijing, P. R. China.
authors: Hui
authors: H
authors: Zhang
authors: Jian
authors: J
authors: Wang
authors: Bo
authors: B
authors: Pang
authors: Rui-xia
authors: RX
authors: Liang
authors: Suping
authors: S
authors: Li
authors: Pei-tang
authors: PT
authors: Huang
authors: Ruoxiang
authors: R
authors: Wang
authors: Leland W K
authors: LW
authors: Chung
authors: Haiyen E
authors: HE
authors: Zhau
authors: Cuifen
authors: C
authors: Huang
authors: Jian-guang
authors: JG
authors: Zhou
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011755:Pyrophosphatases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014105:Tosyl Compounds / Q000494:pharmacology; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D016373:DNA, Antisense; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; D051058:Oncogene Protein v-akt; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases