Inhibition of cell proliferation by 17beta-estradiol and heregulin beta1 in estrogen receptor negative human breast carcinoma cell lines.
Heregulin (HRG) and 17beta-estradiol (E2) interactions that modulate growth of breast cancer cell lines have recently been demonstrated. We examined the ability of heregulin beta1 (HRGbeta1) and 17beta-estradiol to modulate the biological behavior of estrogen receptor (ER) negative human breast cancer cell lines (AU-565). The proliferation of AU-565, MBA-MB231, and SKBR3 cells was additively inhibited by treatment with 17beta-estradiol (10(-6) M) and HRGbeta1 (10 ng/ml). 17-beta estradiol did not support the transcriptional activation of a reporter gene construct containing an estrogen response element transfected into AU-565 cells. This finding suggested functional endogenous ER was not present in AU-565 cells. However, the cells contained a high number of low affinity estrogen binding sites. 17beta-estradiol only slightly decreased basal tyrosine phosphorylation of ErbB-2 and ErbB-3. Estrogen and HRGbeta1 treatment resulted in an increase of c-myc mRNA. We conclude that 17beta-estradiol and HRGbeta1, in combination, potently inhibit cell proliferation of three ER negative breast carcinoma cell lines.
Yoo
J Y
JY
Molecular and Cellular Biology Program, University of Maryland at Baltimore, School of Medicine, USA.
Lessor
T
T
Hamburger
A W
AW
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020893:Receptor, ErbB-3; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D002352:Carrier Proteins; D006023:Glycoproteins; D006131:Growth Inhibitors; D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins; C087230:heregulin beta1; D004958:Estradiol; D066246:ErbB Receptors; D020893:Receptor, ErbB-3