title: Bmi1 promotes prostate tumorigenesis via inhibiting p16(INK4A) and p14(ARF) expression.
abstract: We report here that the polycomb group protein Bmi1 promotes prostate tumorigenesis. Bmi1 is detected at higher levels in androgen-independent PC3 and DU145 than in androgen-dependent LNCaP prostate cancer (CaP) cells. Ectopic Bmi1 enhanced the expression of human telomerase reverse transcriptase (hTERT) and suppressed the exression of p16(INK4A) and p14(ARF) in CaP cells. Consistent with these observations, immunohistochemical staining of 51 cases of primary CaP specimens revealed 1.4 fold (p=0.014) and 1.3 fold (p=0.051) higher levels of Bmi1-positive cells in carcinoma compared to normal prostatic epithelial cells and PIN, respectively. In primary CaPs, Bmi1 expression was associated with a reduction in p16(INK4A) and p14(ARF). Furthermore, in comparison to empty vector-transfected cells, Bmi1-expressing DU145 cells formed significantly larger tumors in NOD/SCID mice. Taken together, we demonstrate that Bmi1 promotes prostate tumorigenesis.
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fan
authors.forename: Lizhi
authors.initials: L
authors.lastname: He
authors.forename: Anil
authors.initials: A
authors.lastname: Kapoor
authors.forename: Aubrey
authors.initials: A
authors.lastname: Gillis
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Rybak
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*
chemical_list: C069077:BMI1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1