Transforming growth factor alpha and beta expression in human colon cancer lines: implications for an autocrine model.
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.
D002460:Cell Line; D003110:Colonic Neoplasms / Q000032:analysis*; D066246:ErbB Receptors / Q000032:analysis; D006801:Humans; D008954:Models, Biological; D008970:Molecular Weight; D010455:Peptides / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors
D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D066246:ErbB Receptors