PI3K-Akt signaling is involved in the regulation of p21(WAF/CIP) expression and androgen-independent growth in prostate cancer cells.
The purpose of this study is to investigate the role of PI3K-Akt signaling in prostate cancer cell growth and androgen receptor (AR)-mediated gene expression. Androgen-dependent LNCaP cells and their androgen-independent counterpart, LNCaP-AI cells, were used. We found that PI3K-Akt signaling is elevated in LNCaP-AI cells compared to that in LNCaP cells and is involved in androgen-independent growth. More importantly, PI3K-Akt signaling enhances AR activity and is involved in the induction of AR target genes, such as p21(WAF/CIP), a gene with anti-apoptosis activity and associated with androgen-independent growth in human prostate cancer. A receptor tyrosine kinase inhibitor also inhibits the PI3K-Akt signaling and compromises AR activity and cell growth. These findings suggest that the PI3K-Akt cell growth survival pathway and its downstream-regulated gene, p21(WAF/CIP), are targets for developing novel therapies against prostate cancer, especially those androgen-independent diseases.
Lu
Shan
S
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0529, USA. shan.lu@uc.edu
Ren
Chengxi
C
Liu
Yin
Y
Epner
Daniel E
DE
D000728:Androgens / Q000502:physiology; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D011944:Receptors, Androgen / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000728:Androgens; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011944:Receptors, Androgen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt