Androgen signaling and post-transcriptional downregulation of Bcl-2 in androgen-unresponsive prostate cancer.
We previously characterized the LNCaP prostate cancer progression model and showed that despite loss of Bcl-2 protein in the androgen-unresponsive LNCaP-unresponsive (UR) cells, these cells maintained an increased resistance to the induction of apoptosis. Since the loss of Bcl-2 protein coincided with the progression to androgen-unresponsiveness, we sought to determine if Bcl-2 expression was regulated through androgen signaling pathways. LNCaP-responsive (R) and -UR cells grown in charcoal-stripped serum conditions for 3 months differentiated to a neuroendocrine (NE)-like morphology. Under these conditions, LNCaP-UR cells regained Bcl-2 protein expression, and LNCaP-R cells overexpressed Bcl-2. Chronic exposure to casodex resulted in differentiation of both LNCaP-R and -UR cells to the NE-type morphology accompanied by a marked downregulation of Bcl-2 protein, while Bax protein levels were unchanged. Downregulation of Bcl-2 was post-transcriptional since Bcl-2 message levels were unchanged in LNCaP cells treated with casodex. These data suggest that Bcl-2 is post-transcriptionally modulated by androgen signaling pathways in LNCaP cells.
Rothermund
C A
CA
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-4525, USA.
Gopalakrishnan
V K
VK
Vishwanatha
J K
JK
D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases