Accession Number : ADA306441

Title :   Spatial Distribution of the EGF Receptor in Regulation of Breast Epithelial Cell Growth and Organization.

Descriptive Note : Annual rept. 1 sep 94-31 Aug 95,

Corporate Author : UTAH UNIV SALT LAKE CITY

Personal Author(s) : Wiley, H. S.

PDF Url : ADA306441

Report Date : SEP 1995

Pagination or Media Count : 16

Abstract : The spatial distribution of the EGF receptor and ligands is necessary for normal organization and proliferation of human mammary epithelial cells. We found that these cells express high levels of EGF receptors. These receptors are rapidly internalized and recycled. Unlike transformed cells, internalization efficiency of normal HMEC is high. These cells also make high levels of EGF, TGF-alpha, HB-EGF and amphiregulin, although TGF-alpha and amphiregulin appear to be the predominant ligands. We transfected cells with a gene encoding an artificial ligand consisting of the mature sequences of EGF (sEGF). Cells expressing sEGF could not be inhibited by antagonistic anti-EGF-R antibodies, apparently because the sEGF was working through an intracrine mechanism. Importantly, cells expressing sEGF could not organize correctly. Also, the ability of HMEC to spread and migrate on the extracellular matrix was dependent of EGF-R occupancy. Our data suggests that the ability to HMEC to spatially sense their environment is dependent on the EGF-R system through an autocrine mechanism. Importantly, these data support our hypothesis that disruptions in the spatial aspects of EGF-R signaling could facilitate the development of breast cancer.

Descriptors :   *EPITHELIUM, *GENES, *CELLS(BIOLOGY), *MAMMARY GLANDS, *BREAST CANCER, SPATIAL DISTRIBUTION, ORGANIZATIONS, CODING, LIGANDS, HYPOTHESES, CANCER.

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE