Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway.
It has been suggested that the helix-loop-helix protein Id-1 plays an important role in tumourigenesis in certain types of human cancer. Previously, we reported that Id-1 was up-regulated during sex hormone-induced prostate carcinogenesis in a Noble rat model (Ouyang et al. (2001) Carcinogenesis, 22, 965-973). In the present study, we investigated the direct effect of Id-1 expression on human prostate cancer cell proliferation by transfecting an Id-1 expression vector into a prostate cancer cell line LNCaP. Ten stable transfectant clones were isolated and the ectopic Id-1 expression resulted in both increased DNA synthesis rate and the percentage of S phase cells. To study the possible mechanisms involved in the Id-1 induced prostate cancer cell growth, we examined the expression of several factors responsible for G(1) to S phase progression. We found that Id-1 expression induced phosphorylation of RB and down-regulation of p16(INK4a) but not p21(Waf1)or p27(Kip1). Our results indicate that the Id-1 induced inactivation of p16(INK4a)/pRB pathway may be responsible for the increased cell proliferation in prostate cancer cells. Given the fact that both Id-1 over-expression and inactivation of p16(INK4a)/pRB are common events in prostate cancer, our results provide a possible mechanism on the molecular basis of prostate carcinogenesis.
Ouyang
Xue Song
XS
Department of Anatomy, Faculty of Medicine, 5/F, Li Shu Fan Building, 5 Sassoon Road, University of Hong Kong, Hong Kong, SAR, China.
Wang
Xianghong
X
Ling
Ming-Tat
MT
Wong
Hing Lok
HL
Tsao
Sai Wah
SW
Wong
Y C
YC
D001769:Blood; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors*; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors