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

Dorothy Walker-Jones, Eva M. Valverius, Marc E. Lippman, Robert B. Dickson, Martha R. Stampfer

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Transforming growth factor-β (TGFβ) 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 TGFβ 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 TGFβ stimulation of EMA expression. The degree of increase in EMA induced by TGFβ was proportional to the level of basal expression in each cell type and appeared to be unrelated to either the number of high affinity TGFβ receptors, or the relative sensitivity to growth inhibition by TGFβ. Therefore, the TGFβ 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 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 TGFβ and SV40 T-transformation in enhancing the expression of EMA, and the possible effect of SV40 T in increasing the responsiveness to TGFβ, may provide a new model for the study of the effect of growth factors in regulating specific gene expression in human breast epithelial cells.

Original languageEnglish (US)
Pages (from-to)6407-6411
Number of pages5
JournalCancer Research
Volume49
Issue number22
StatePublished - Nov 15 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Walker-Jones, D., Valverius, E. M., Lippman, M. E., Dickson, R. B., & Stampfer, M. R. (1989). Stimulation of Epithelial Membrane Antigen Expression by Transforming Growth Factor-β in Normal and Oncogene-transformed Human Mammary Epithelial Cells. Cancer Research, 49(22), 6407-6411.