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

Abstract

We have characterized the expression of transforming growth factor α (TGFα) and its receptor, the epidermal growth factor receptor (EGF-R), in normal and 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/TGF α 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. © 1989 by The Endocrine Society.