Autocrine Growth Loop of The Epidermal Growth Factor Receptor in Normal and Immortalized Human Bronchial Epithelial Cells |
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Authors: | Ming-Sound Tsao Hong Zhu Jean Viallet |
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Affiliation: | aDepartment of Pathology, Montreal General Hospital/Research Institute, Montreal, Quebec, Canada, H3G 1A4;bMcGill University, Montreal, Quebec, Canada, H3G 1A4;cCentre d'oncologie, Hôpital Notre Dame, 1560 est, Rue Sherbrooke, Montreal, Quebec, Canada, H2L 4M1 |
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Abstract: | Epidermal growth factor (EGF) is a potent growth factor for human normal bronchial epithelial (HBE) cells and lung cancer cells, which often demonstrate an EGF receptor (EGFR) autocrine loop. We have found that HBE cells are capable of proliferating in basal medium without EGF supplementation, and this suggests the probable presence of an active EGFR autocrine loop in non-neoplastic HBE cells. Northern blot hybridization shows that the parental and immortalized HBE cells express comparable and high levels of mRNA for EGFR, transforming growth factor-alpha (TGF-α), and amphiregulin (AR), but not EGF. Incubation with neutralizing monoclonal antibodies (mAb) against EGFR partially inhibits the growth of these cells. Immunohistochemistry shows that HBE cells express the TGF-α peptidein vitroandin vivo,however, neutralizing mAbs against TGF-α fail to inhibit their proliferation. In contrast, AR stimulates the growth of HBE cells. Thus, several EGF-family ligands appear to be involved functionally in the EGFR autocrine growth loop in HBE cells. |
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