The estrogenic and antiestrogenic properties of tamoxifen in GH4C1 pituitary tumor cells are gene specific.
We have examined the effects of the antiestrogen tamoxifen (TAM) and the estrogen 17 beta-estradiol (E2) on several estrogen-regulated responses in GH4C1 pituitary tumor cells. After 5 days of treatment with either TAM (1.0 microM) or E2 (1.0 nM), the level of PRL mRNA was markedly increased when measured by the cytosolic dot blot procedure. In contrast, only E2 was able to increase the levels of beta-actin mRNA and cytosolic protein, suggesting that this estrogen may stimulate cell proliferation over the course of treatment. This apparent difference in the abilities of TAM and E2 to stimulate GH4C1 cell proliferation was examined directly. TAM had no effect on cell proliferation as evidenced by its inability to increase cellular DNA or deoxythymidine triphosphate incorporation by nuclei isolated from treated cells. In contrast, E2 stimulated cell proliferation as evidenced by increases in cellular DNA and deoxythymidine triphosphate incorporation by isolated nuclei. The abilities of TAM and E2 to induce progesterone receptor (PR) and PR mRNA were also examined. TAM was unable to increase the levels of PR or PR mRNA, whereas E2 was effective in both of these regards. When added in combination with E2, TAM acted as a classical antiestrogen, partially blocking the induction of PR by E2. To determine whether the inabilities of TAM to stimulate cell proliferation and induce PR were a function of TAM concentration, dose-response experiments were performed. TAM at concentrations ranging from 10(-8)-10(-6) M was effective in inducing PRL mRNA, but at none of the tested concentrations was TAM effective in stimulating cell proliferation or inducing PR.(ABSTRACT TRUNCATED AT 250 WORDS)
Shull
J D
JD
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.
Beams
F E
FE
Baldwin
T M
TM
Gilchrist
C A
CA
Hrbek
M J
MJ
D000199:Actins / Q000235:genetics*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D000199:Actins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol; D011388:Prolactin; D013936:Thymidine