Relationship of levels and kinetics of H-ras expression to transformed phenotype and loss of TGF-beta 1-mediated growth regulation in intestinal epithelial cells.
Immortalized, nontumorigenic rat intestinal epithelial cells (IEC-18) can be transformed to tumorigenicity by expression of an activated human H-ras gene. Here we describe the characteristics of an IEC-18 cell line in which the activated human H-ras gene has been introduced under the control of the steroid-sensitive promoter of the mouse mammary tumor virus long-terminal repeat. The clonal cell line (IEC-18 C125) is phenotypically normal in the absence of the transcription inducer, dexamethasone, and transformed when treated with high levels of inducer. Transformed morphology and growth characteristics are dependent on levels of H-ras expression. IEC-18 C125 cells have been used to demonstrate a general relationship (dose and kinetic) between H-ras expression and loss of TGF-beta 1-mediated growth regulation. This effect occurs concomitantly with a ras-dependent change in the profile of TGF-beta 1 binding proteins.
Zhao
J
J
Ontario Cancer Institute, Toronto, Canada.
Buick
R N
RN
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D003907:Dexamethasone / Q000494:pharmacology; D004848:Epithelium; D015870:Gene Expression; D011905:Genes, ras; D007422:Intestines; D007700:Kinetics; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D003907:Dexamethasone