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Stimulation of Epithelial Membrane Antigen Expression by Transforming Growth Factor-ß in Normal and Oncogene-transformed Human Mammary Epithelial Cells¹

Department of Zoology, Howard University, Washington, DC 20059 [D. W-J.]; Vincent Lombardi Cancer Research Center, Georgetown University Hospital, Washington, DC 20007 [E. M. V., M. E. L., R. B. D.]; and the Lawrence Berkeley Laboratory, University of California, Berkeley, California 94720 [M. R. S.]

Transforming growth factor-ß (TGFß) appears to play a role in regulating the expression of tissue-specific proteins in human mammary epithelial cells (HMEC), regardless of the state of malignant transformation. We demonstrated this by utilizing a series of normal, immortalized, and oncogene-transformed (SV40 T and v-Ha-ras) HMEC derived from one individual, and assaying for expression of a milk fat globule/epithelial membrane antigen (EMA) reactive with E29/EP1 monoclonal antibody.

EMA was increased by TGFß in all HMEC examined. This effect appeared to be dose-dependent between 5 and 15 ng/ml in the normal, immortalized, and v-Ha-ras-transformed cells but saturated at 5 ng/ml in the SV40 T-transformed cells. The SV40 T-transformed cells showed both enhanced basal expression of EMA and increased sensitivity to TGFß stimulation of EMA expression. The degree of increase in EMA induced by TGFß was proportional to the level of basal expression in each cell type and appeared to be unrelated to either the number of high affinity TGFß receptors, or the relative sensitivity to growth inhibition by TGFß. Therefore, the TGFß effect on EMA appears to be modulated at a level beyond receptors in these cells. EMA expression was also stimulated by sodium butyrate and dexamethasone (both differentiating agents) in some of the HMEC.

The effect of butyrate on EMA expression is consistent with previous findings in which butyrate selectively enhanced production of milk fat globule antigens in the breast tumor cell line MCF-7, ZR-75-1, MDA-MB-134, and MDA-MB-468 cells. The coupled effects of TGFß and SV40 T-transformation in enhancing the expression of EMA, and the possible effect of SV40 T in increasing the responsiveness to TGFß, may provide a new model for the study of the effect of growth factors in regulating specific gene expression in human breast epithelial cells.

¹ Presented, in part, at the meeting of the American Association for Cancer Research, New Orleans, May 1988.

² To whom requests for reprints should be addressed, at Vincent Lombardi Cancer Research Center, Georgetown University Hospital, 3900 Reservoir Road, NW, Washington, DC 20007.

Received 3/28/89. Revised 8/16/89. Accepted 8/21/89.