title: Transforming growth factors produced by normal and neoplastically transformed rat liver epithelial cells in culture.
abstract: The secretion of transforming growth factors (TGFs) alpha and beta by normal, chemically transformed, and malignant rat liver epithelial cell lines was investigated. The WB-F344 normal cultured rat liver epithelial cell line does not secrete an epidermal growth factor-like (putatively TGF-alpha) activity, but several clonal cell strains derived from WB-F344 cells which had been treated with N-methyl-N'-nitro-N-nitrosoguanidine, especially those that expressed high levels of gamma-glutamyl transpeptidase, secreted TGF-alpha-like activity into their conditioned media. Cell lines obtained from tumors which were produced by these cell strains varied in their abilities to secrete TGF-alpha, even though they all expressed high levels of gamma-glutamyl transpeptidase activity. When two of the non-TGF-alpha-secreting tumor cell lines were transplanted into isogeneic rats, the tumors that formed contained high levels of TGF-alpha-like activity. Although epidermal growth-factor (hence, TGF-alpha also) inhibited the proliferation of several of these tumor cell lines in monolayer cultures, this growth factor often paradoxically stimulated the anchorage-independent growth of the same cell lines. In contrast to TGF-alpha-like activity, all cell lines/strains released TGF-beta activity into their conditioned media. However, while both normal or chemically transformed cell strains typically produced the inactive form of TGF-beta, the tumor cell lines tended to produce activated TGF-beta de novo. Anchorage-independent growth of cell lines that produced active TGF-beta was either stimulated, inhibited, or unaffected by TGF-beta. Cell lines that were inhibited by TGF-beta concurrently produced TGF-alpha which was usually able to overcome the negative "autocrine" effect of TGF-beta. We conclude that both TGF-alpha and TGF-beta, singly or in combination, are variously involved in the growth of transformed rat liver epithelial cells. TGF-alpha has a predominantly positive autocrine action on the growth of rat liver epithelial tumor cell lines. The "paracrine" effect of TGF-beta may be at least as important as its autocrine effect in the growth of these transformed epithelial cell lines.
authors.affiliation: Department of Pathology, Montreal General Hospital and McGill University, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.forename: M S
authors.initials: MS
authors.lastname: Tsao
authors.forename: J W
authors.initials: JW
authors.lastname: Grisham
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D015291:Transforming Growth Factors
chemical_list: D006133:Growth Substances; D007328:Insulin; D009363:Neoplasm Proteins; D010455:Peptides; D008769:Methylnitronitrosoguanidine; D015291:Transforming Growth Factors; D066246:ErbB Receptors