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Role of Epidermal Growth Factor Receptors and Their Ligands in Normal Mammary Epithelial and Breast Cancer Cells

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Annual rept. 1 Jul 95-30 Jun 96

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Epidermal growth factor EGF and transforming growth factor a TGF exert their effects through membrane-associated EGF receptors EGFR. Although their mechanisms of action are not completely understood, these growth factors and their receptors are physiological regulators of normal mammary gland development, and are often overexpressed in estrogen receptor negative breast cancers. Initially, we examined the effects of EGF and TGF on the in vitro development of normal rat mammary epithelial cells MEC. PD158780, a potent and selective inhibitor of the tyrosine kinase domain of the EGFR, was then used to demonstrate that EGFR signaling was required, at least in part, for normal MEC proliferation, survival, and functional differentiation. In addition, normal rat mammary fibroblasts MFC were used to examine rapid signal transduction events including tyrosine phosphorylation protein profiles and MAPK phosphorylation in response to EGFR activation by EGF or TGF. PD15878O was then employed to confirm that the signal transduction responses were EGFR-dependent. We will continue to examine the roles that EGFR play in the development of normal MEC cultured alone as well as MEC co-cultured with mammary fibroblasts, pre-adipocytes, or mature adipocytes, and then to examine their role during rat mammary tumor progression and metastasis. Ultimately, we hope that this data will help to identify new therapeutic targets and develop effective therapies to treat patients with estrogen receptor negative breast cancer.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research
  • Organic Chemistry
  • Physical Chemistry

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