TRANSFORMING GROWTH FACTOR-ALPHA AND FACTOR-BETA EXPRESSION IN HUMAN-COLON CANCER LINES - IMPLICATIONS FOR AN AUTOCRINE MODEL

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  • 1 September 1987
    • journal article
    • research article
    • Vol. 47  (17) , 4590-4594
Abstract
Three human colon cancer lines (SW480, SW620, WIDR) secrete different levels of transforming growth factor .beta. (TGF.beta.)-like and transforming growth factor .alpha. (TGF.alpha.)/epidermal growth factor (EGF)-like molecules into serum-free conditioned media as measured by competing activity in TGF.beta. and EGF radioreceptor assays. SW480 cells, the highest producers of TGF.beta.-like activity, lack detectable TGF.beta. receptors while SW620 cells, the highest producers of TGF.alpha./EGF-like activity, lack EGF receptors. This study investigated the production of these growth factors at the mRNA level and examined the mechanism of loss of detectable receptors. Using complementary DNA probes for TGF.beta. and TGF.alpha., it was demonstrated that mRNA levels correlated with the amounts of TGF.beta. and TGF.alpha. produced; TGF.beta. gene expression was highest in SW480 cells and TGF.alpha. gene expression was highest in SW620 cells. Acid washing of the SW480 cells prior to performing the TGF.beta. binding assay resulted in the unmasking of substantial levels of TGF.beta. receptors. Neither acid washing nor preincubation with suramin uncovered EGF receptors in SW620 cells. Also, and in contrast to the other two lines, EGF receptor expression could not be detected in SW620 cells by Northern gel analysis of receptor messenger RNA or by immunological analysis of receptor protein. Thus two distinct mechanisms (occupation of TGF.beta. receptor in SW480 cells, or absence of EGF receptor in SW620 cells) explain the lack of detectable TGF.beta. and EGF receptors in the binding assays. The autocrine hypothesis remains viable for TGF.beta. in SW480 cells but not for TGF.alpha. in SW620 cells; this would not discount a paracrine role in this latter case.