Effects of transforming growth factors and regulation of their mRNA levels in two human endometrial adenocarcinoma cell lines.
The effects of the transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) on the growth of cells from 2 endometrial cancer lines, Ishikawa and HEC-50 were evaluated by measuring rates of DNA synthesis and changes in cell numbers during culture. EGF at 17 and 1.7 nM concentrations consistently enhanced HEC-50 cell proliferation. TGF-beta 1 inhibited Ishikawa cell proliferation but, unexpectedly for epithelium-derived cells, stimulated HEC-50 cell growth. This effect is of interest as it indicates that endometrial cells can acquire an altered responsiveness to a growth inhibitor during the process of malignant transformation. Northern blot analyses showed expression of TGF-alpha, TGF-beta 1 and EGF receptors mRNA in both cell lines. Neither estradiol (E2) nor 4-hydroxytamoxifen (OHTam) affected mRNA levels for either TGF-alpha or TGF-beta in HEC-50 cells, a line unresponsive to E2 for proliferation. In Ishikawa cells, previously shown to respond to both E2 and OHTam by increasing proliferation rates, E2 increased TGF-alpha mRNA and reduced TGF-beta mRNA levels. OHTam lowered the levels of both mRNA species, although the effect was greater on TGF-beta than TGF-alpha mRNA. These data are consistent with, but do not prove, the existence of a possible autocrine regulation by TGF-alpha and TGF-beta of human cancer cell proliferation, which might be under E2 influence in Ishikawa cells.
Anzai
Y
Y
Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, NY 10029.
Gong
Y
Y
Holinka
C F
CF
Murphy
L J
LJ
Murphy
L C
LC
Kuramoto
H
H
Gurpide
E
E
D000230:Adenocarcinoma; D015152:Blotting, Northern; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D016889:Endometrial Neoplasms; D004815:Epidermal Growth Factor / Q000235:genetics / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; C016601:afimoxifene; D004815:Epidermal Growth Factor; D004247:DNA