Expression of TGF‐α/EGF and TGF‐p receptors in human colon carcinoma cell lines

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Abstract
Previous studies have established that colon carcinoma cells secrete several polypeptide growth factors, including TGF-α/EGF and TGF-ß, suggesting that these and related molecules function in an autocrine/paracrine fashion to modulate tumor-cell growth. To investigate this possibility, we have studied the expression of transforming growth factor receptors in a panel of human colon carcinoma cell lines and in several untransformed epithelial cell populations. The results have revealed that neoplastic colon cells express receptors for both TGF-α/EGF and TGF-ß. Immunoprecipitation identified the TGF-α/EGF receptor as a structurally intact 170-kDa protein. No evidence for over-expression was found. TGF-α (and EGF) enhanced receptor autophosphorylation, indicating that these receptors were biochemically functional. TGF-ß blocked DNA synthesis in non-neoplastic epithelial cells but not in tumorigenic colon populations. There was no correlation with TGF-ß receptor number or dissociation constant. However, chemical cross-linking studies revealed a TGF-ß receptor subtype of 75 kDa in 3 of the 4 colon carcinoma cells which was undetectable in normal IEC epithelial cultures, suggesting a possible association between 75-kDa receptor expression and refractoriness to growth inhibition of TGF-ß. Together, these data support the concept that locally-produced growth regulators can function in an autocrine or paracrine manner to influence the proliferation of colon carcinoma cells.