Epidermal growth factor dependence and TGFα autocrine growth regulation in primary rat tracheal epithelial cells

✍ Scribed by Patrice C. Ferriola; Alice T. Robertson; David W. Rusnak; Richard Diaugustine; Paul Nettesheim

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 880 KB
• Volume: 152
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041520211

✦ Synopsis

We have examined dependence of primary rat tracheal epithelial (RTE) on exogenous epidermal growth factor (EGF) and determined whether a T L F a autocrine pathway is operating in these cells. Primary KTE cells plated in serum free media (SFM) without EGF and bovine pituitary factor (BPE) show little proliferation compared to cultures propagated in media containing EGFiBPE (CSFM). Removal of EGFiBPE shortly after plating, however, results in significant proliferation, although plateau cell densities are reduced and cell morphology is significantly altered compared to cells propagated in CSFM. Addition of ECF and/or BPE to cultures propagated in SFM minus ECFIBPE restores maximum cell density. The concentration of TGFa peptide in media conditioned by cells propagaied without EGFIBPE is lower than the concentration in the media of CSFM cultures. TGFa mKNA and protein levels are also significantly lower in cells late in culture compared to logarithmically growing cells regardless of the presence or absence of EGF/BPE. The proliferation of primary RTE cells propagated without EGFiBPE is inhibited by neutralizing TGFa antiserum and by a tyrphostin compound that blocks TGFaiEGF receptor tyrosine kinase activity. These results indicate that primary RTE cells utilize T t i F a as an autocrine growth factor and that the autocrine pathway is regulated as a function of growth state of the cells. However, this pathway does not provide growth autonomy to primary RTE cells, since cultures remain dependent on exogenous EGFiBPE for sustained proliferation.