Effects of Ca++ mobilization on expression of androgen-regulated genes: interference with androgen receptor-mediated transactivation by AP-I proteins.
BACKGROUND
The adult prostate is maintained through an equilibrium between cell growth and death rates. Androgen deprivation induces an increase in intracellular Ca++, AP-1 gene expression of androgen-inducible genes.


METHODS
Northern blot analysis, band-shift assays, and transient cotransfection assays were used to study the effects of Ca++ mobilizer A23187 on gene expression in human prostate cancer cells.


RESULTS
A23187 repressed androgen-upregulated mRNAs for prostate-specific antigen (PSA) and hKLK2, and rapidly induced mRNA levels for c-fos and c-jun. AP-1 protein-DNA binding activities were elevated after A23187 treatments. Androgen receptor (AR)-mediated induction of chloramphenicol acetyltransferase (CAT) reporter was repressed by AP-1 proteins.


CONCLUSIONS
The repression of AR-mediated induction of PSA and hKLK2 genes by Ca++ mobilizers is due to the interference of AR transactivation activity by AP-1 proteins.
Murtha
P E
PE
Department of Urology, Mayo Clinic/Foundation, Rochester, MN 55909, USA.
Zhu
W
W
Zhang
J
J
Zhang
S
S
Young
C Y
CY
D000728:Androgens / Q000494:pharmacology*; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D016762:Genes, fos / Q000235:genetics* / Q000502:physiology; D016758:Genes, jun / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007610:Kallikreins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011944:Receptors, Androgen / Q000502:physiology*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology; D014162:Transfection
D000728:Androgens; D007476:Ionophores; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; D000001:Calcimycin; D015500:Chloramphenicol O-Acetyltransferase; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D002118:Calcium