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Induction of Estrogen-Regulated Genes Differs in Immortal and Tumorigenic Human Mammary Epithelial Cells Expressing a Recombinant Estrogen Receptor

Dana Farber Cancer Institute Boston, Massachusetts 02115

Address requests for reprints to: Dr. Ruth Sager, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115.

Abstract

Studies on estrogen receptor (ER)-positive human breast cancer cell lines have shown that estrogen treatment positively modulates the expression of the genes encoding transforming growth factor- (TGF), 52-kDa cathepsin-D, and pS2. To determine whether these genes would be similarly regulated by estrogens in normal human mammary epithelial cells, we stably transfected immortal nontumorigenic human mammary epithelial cells with an ER-encoding expression vector. ER-negative tumor cells were also transfected for comparison. Levels of TGF and 52-kDa cathepsin-D mRNA were enhanced by estrogen treatment of both ER-transfected immortal and tumorigenic cells, demonstrating that the ER by itself is sufficient to elicit estrogenic regulation of the expression of these genes.

In contrast, expression of the pS2 gene was detected only in the ER-transfected tumor cells. The ER in both cell lines is capable of recognizing the pS2 promoter, however, since estrogen enhanced the activity of an introduced pS2-CAT reporter plasmid in transient expression analyses. These and other experiments with somatic cell hybrids between the immortal cells and ER+/pS2+ MCF-7 tumor cells, where pS2 gene expression is extinguished, support the conclusion that the immortal nontumorigenic cells encode gene products that block endogenous pS2 expression. These results also imply that such repressors are not active in the tumor cells.

FOOTNOTES

This work was supported by USPHS Grant CA-39814 from the NCI.

^* Present address: Berlex Biosciences, Alameda, California 94501.

Received for publication May 13, 1991. Revision received August 12, 1991. Accepted for publication August 12, 1991.

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