cDNA microarray analysis identifies genes induced in common by peptide growth factors and androgen in human prostate epithelial cells.
Prostate cancer cells initially require androgen for continued proliferation, but invariably become androgen independent or unresponsive and recur after treatment by androgen ablation. Exploitation of common signaling components downstream of their specific receptors (i.e., androgen receptor (AR), insulin-like growth factor 1 (IGF-1) receptor, and epidermal growth factor (EGF) receptor) could provide a mechanism by which androgen independent cells survive and proliferate. Our objective was to design and implement prostate enriched cDNA microarrays to identify genes induced in prostate epithelial cells in a similar temporal pattern by both androgen and IGF or EGF. AR positive and AR negative human prostate epithelial cells of the M12 line were exposed in parallel to DHT, EGF, or IGF for 0, 6, or 24 h. RNA extracted from each of these groups was analyzed by cDNA microarrays composed of a unique set of 6373 prostate-derived cDNA clones from the Prostate Expression Database (PEDB). We observed statistically significant changes in 20 genes induced in common after 6 and 24 h exposure to androgen or these growth factors, and validated the microarray results by RT-PCR for three or four of these genes: v-myc, isocitrate dehydrogenase, and calnexin. Androgen response element binding motifs were identified in the upstream sequence in 16 of these 20 genes. These results provide comprehensive and unique insights into potential mechanisms by which peptide growth factors provide alternate pathways to control prostate epithelial cell proliferation in malignant states.
York
Timothy P
TP
Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Plymate
Stephen R
SR
Nelson
Peter S
PS
Eaves
Lindon J
LJ
Webb
Heather D
HD
Ware
Joy L
JL
D014408:Biomarkers, Tumor / Q000032:analysis; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I