Akt in prostate cancer: possible role in androgen-independence.
Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), has often been implicated in prostate cancer. Studies in prostate tumor cell lines revealed that Akt activation is probably important for the progression of prostate cancer to an androgen-independent state. Investigations of human prostate cancer tissues show that although there is neither Akt gene amplification nor enhanced protein expression in prostate cancer compared to normal tissue, poorly differentiated tumors exhibit increased expression of a phosphorylated (activated) form of Akt compared to normal tissue, prostatic intraepithelial neoplasia (PIN) or well-differentiated prostate cancer. Akt phosphorylation is accompanied by the inactivation of ERK, a member of the mitogen activated protein kinase (MAPK) family. In this article, we postulate that Akt promotes androgen-independent survival of prostate tumor cells by modulating the expression and activation of the androgen receptor (AR).
Ghosh
Paramita M
PM
Department of Surgery, University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, Audie L. Murphy Veterans Administration Hospital, San Antonio, TX 78229-3900, USA.
Malik
Shazli
S
Bedolla
Roble
R
Kreisberg
Jeffrey I
JI
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen / Q000502:physiology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D000728:Androgens; D020928:Mitogen-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen; D025521:Tumor Suppressor Proteins; D018631:ras Proteins; C494918:AKT1 protein, human; C494929:PTEN protein, human