Expression of estrogen receptors in estrogen receptor-negative human breast carcinoma cells: modulation of epidermal growth factor-receptor (EGF-R) and transforming growth factor alpha (TGF alpha) gene expression.
A number of studies suggest that an inverse correlation exists between the epidermal growth factor-receptor and the estrogen receptor expression in primary human breast carcinoma as well as in established human breast carcinoma cell lines. Recent studies suggest that the epidermal growth factor-receptor does not regulate the estrogen receptor gene expression. Whether the estrogen receptor regulates the epidermal growth factor-receptor gene expression is not known. We addressed this question by stably transfecting the estrogen receptor cDNA into the estrogen receptor-negative human breast carcinoma cell line MDA-MB-231. Constitutive expression of functional estrogen receptors in the transfectants resulted in increased mRNA levels of both epidermal growth factor-receptor and transforming growth factor alpha. Estradiol treatment of transfected cells, although enhancing transforming growth factor alpha mRNA levels, did not modulate epidermal growth factor-receptor mRNA levels. The estrogen receptor-transfected cells grown in estrogenic regular medium, however, exhibited lower constitutive levels of epidermal growth factor-receptor mRNA than in steroid-stripped medium, suggesting that estrogens coupled with some factors normally present in the regular medium may indeed downmodulate epidermal growth factor-receptor mRNA. Sodium butyrate treatment enhanced epidermal growth factor-receptor mRNA levels in nontransfected cells grown in regular estrogenic as well as in steroid stripped medium. Sodium butyrate enhancement of epidermal growth factor-receptor mRNA levels was completely abolished in estrogen receptor-transfected cells grown in regular estrogenic medium and blunted in steroid stripped medium. Using various epidermal growth factor-receptor gene promoter-CAT constructs in transient transfection assays, we further demonstrate that sodium butyrate enhanced transcription of the epidermal growth factor-receptor gene. The putative sodium butyrate responsive element(s) appears to localize within the proximal 384 bp of the epidermal growth factor-receptor gene promoter region. Although the interactions between estrogen receptor and epidermal growth factor-receptor are rather complex, taken together, our data suggest that estrogen receptor can indeed modulate the epidermal growth factor-receptor mRNA expression.
Sheikh
M S
MS
Department of Medicine, University of Maryland Cancer Center, University of Maryland School of Medicine, Baltimore.
Shao
Z M
ZM
Chen
J C
JC
Li
X S
XS
Hussain
A
A
Fontana
J A
JA
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002999:Clone Cells; D015536:Down-Regulation; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D002087:Butyrates; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha; D020148:Butyric Acid; D004958:Estradiol; D066246:ErbB Receptors