Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16INK4a/pRB pathway

• Published in: Carcinogenesis (New York) Vol. 23; no. 5; pp. 721 - 725
• Main Authors: Ouyang, Xue Song, Wang, Xianghong, Ling, Ming-Tat, Wong, Hing Lok, Tsao, Sai Wah, Wong, Y.C.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2002; Oxford Publishing Limited (England)
• Subjects: 5′-bromo-2′-deoxyuridine; Biological and medical sciences; BrdU; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; FCS; fetal calf serum; Fundamental and applied biological sciences. Psychology; helix–loop–helix; HLH; Molecular and cellular biology; Human; Cell proliferation; Helix loop helix structure; Urinary system disease; Prostate disease; Retinoblastoma gene; DNA synthesis; Malignant tumor; Gene expression; Carcinogenesis; In vitro; CDKN2 gene; Signal transduction; S Phase; Cell cycle; Established cell line; Transcription factor; Mechanism of action; Male genital diseases; Prostate; Tumor cell
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/23.5.721

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 G1 to S phase progression. We found that Id-1 expression induced phosphorylation of RB and down-regulation of p16INK4a but not p21Waf1or p27Kip1. Our results indicate that the Id-1 induced inactivation of p16INK4a/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 p16INK4a/pRB are common events in prostate cancer, our results provide a possible mechanism on the molecular basis of prostate carcinogenesis.