Expression of TGF-alpha/EGF and TGF-beta receptors in human colon carcinoma cell lines.
Previous studies have established that colon carcinoma cells secrete several polypeptide growth factors, including TGF-alpha/EGF and TGF-beta, 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-alpha/EGF and TGF-beta. Immunoprecipitation identified the TGF-alpha/EGF receptor as a structurally intact 170-kDa protein. No evidence for over-expression was found. TGF-alpha (and EGF) enhanced receptor autophosphorylation, indicating that these receptors were biochemically functional. TGF-beta blocked DNA synthesis in non-neoplastic epithelial cells but not in tumorigenic colon populations. There was no correlation with TGF-beta receptor number or dissociation constant. However, chemical cross-linking studies revealed a TGF-beta 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-beta. 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.
Murthy
U
U
Department of Cell Biology, Smith Kline and French Laboratories, King of Prussia, PA 19406-2799.
Anzano
M A
MA
Greig
R G
RG
D002277:Carcinoma / Q000032:analysis* / Q000473:pathology; D003110:Colonic Neoplasms / Q000032:analysis* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000032:analysis*; D066246:ErbB Receptors / Q000032:analysis*; D006801:Humans; D011956:Receptors, Cell Surface / Q000032:analysis*; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors