Transforming growth factor α production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells

Eva M. Valverius, Susan E. Bates, Martha R. Stampfer, Robin Clark, Frank McCormick, David S. Salomon, Marc E. Lippman, Robert B. Dickson

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

We have characterized the expression of transforming growth factor α (TGFα) and its receptor, the epidermal growth factor receptor (EGF-R), in normal an malignantly transformed human mammary epithelial cells. Human mammary epithelial cells were derived from a reduction mammoplasty (184), immortalized by benzo-a-pyrene (184A1N4), and further transformed by the oncogenes simian virus 40 T (SV40 T), v-Ha-ras, and v-mos alone or in combination using retroviral vectors. 184 and 184A1N4 cells require EGF for anchorage-dependent clonal growth. In mass culture, they secrete TGFα at high concentrations and exhibit an attenuated requirement for exogenous EGF/TGFα. SV40 T transformed cells have 4-fold increased EGF-R, have acquired the ability to clone in soft agar with EGF/TGFα supplementation, but are not tumorigenic. Cells transformed by v-mos or v-Ha-ras are weakly tumorigenic and capable of both anchorage dependent and independent growth in the absence of EGF/TGFα. Cells transformed by both SV40 T and v-Ha-ras are highly tumorigenic, are refractory to EGF/TGFα, and clone with high efficiency in soft agar. The expression of v-Ha-ras is associated with a loss of the high (but not low) affinity binding component of the EGF-R. Malignant transformation and loss of TGFα/EGF responsiveness did not correlate with an increase in TGFα production. Thus, TGFα production does not appear to be a tumor specific marker for human mammary epithelial cells. Differential growth responses to EGF/TGFα, rather than enhanced production of TGFα, may determine the transition from normal to malignant human breast epithelium.

Original languageEnglish (US)
Pages (from-to)203-214
Number of pages12
JournalMolecular Endocrinology
Volume3
Issue number1
DOIs
StatePublished - Jan 1989

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Valverius, E. M., Bates, S. E., Stampfer, M. R., Clark, R., McCormick, F., Salomon, D. S., Lippman, M. E., & Dickson, R. B. (1989). Transforming growth factor α production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells. Molecular Endocrinology, 3(1), 203-214. https://doi.org/10.1210/mend-3-1-203