Androgen regulation of prolactin-receptor gene expression in MCF-7 and MDA-MB-453 human breast cancer cells.
Lactogenic hormones which bind to the PRLR are likely to be growth-stimulatory in human breast-cancer cells. Oestrogen and progesterone control cellular expression of the PRLR; however, elevated androgen levels in some breast-cancer patients raised the possibility that androgens may also influence breast-cancer sensitivity to lactogenic hormones. This study investigated whether androgens could affect expression of the PRLR in the MCF-7 breast-cancer cell line. PRLR binding activity was increased approximately 2-fold by treatment for 24 hr with 10 nM R1881, TEST, DHT, MPA and ORG 2058. Northern analysis indicated that DHT also increased the level of PRLR mRNA. The antiprogesterone, RU 38486, displaced tritiated ORG 2058 binding but not tritiated DHT binding to MCF-7 cells; it completely antagonized ORG 2058 and partially antagonized R1881 induction of the PRLR, but had no effect on induction by DHT. The anti-androgen, RU 23908, displaced tritiated DHT binding but not tritiated ORG 2058 binding, and antagonized DHT and R1881 induction of PRLR but not induction of the PRLR by ORG 2058. These data indicated that ORG 2058 acting via the PR and DHT acting via the AR were able to induce PRLR expression in MCF-7 cells. In MDA-MB-453 cells, which express the AR but not the ER or PR, DHT and R1881 increased PRLR binding to 150% of control values at 0.1 nM. ORG 2058 was ineffective, demonstrating androgen induction of PRLR in the absence of PR and ER. These data indicate that PRLR can be regulated by androgens in MCF-7 and MDA-MB-453 human breast-cancer cells.
Ormandy
C J
CJ
Cancer Biology Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia.
Clarke
C L
CL
Kelly
P A
PA
Sutherland
R L
RL
D000728:Androgens / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D011282:Pregnenediones / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000728:Androgens; D011282:Pregnenediones; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D013196:Dihydrotestosterone; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D015735:Mifepristone