Inhibition of cell proliferation by 17 beta-estradiol and heregulin beta 1in estrogen receptor negative human breast carcinoma cell lines

Heregulin (HRG) and 17 beta-estradiol (E2) interactions that modulate growt h of breast cancer cell lines have recently been demonstrated, We examined the ability of heregulin beta 1 (HRG beta 1) and 17 beta-estradiol to modul ate the biological behavior of estrogen receptor (ER) negative human breast cancer cell lines (AU-565). The proliferation of AU-565, MBA-MB231, and SK BR3 cells was additively inhibited by treatment with 17 beta-estradiol (10( -6) M) and HRG beta 1 (10 ng/ml), 17-beta estradiol did not support the tra nscriptional activation of a reporter gene construct containing an estrogen response element transfected into AU-565 cells. This finding suggested fun ctional endogenous ER was not present in AU-565 cells. However, the cells c ontained a high number of low affinity estrogen binding sites. 17 beta-estr adiol only slightly decreased basal tyrosine phosphorylation of ErbB-2 and ErbB-3. Estrogen and HRG beta 1 treatment resulted in an increase of c-myc mRNA. We conclude that17 beta-estradiol and HRG beta 1, in combination, pot ently inhibit cell proliferation of three ER negative breast carcinoma cell lines.