Characterization of transforming growth factor-beta-resistant subclones isolated from a transforming growth factor-beta-sensitive human colon carcinoma cell line.
Previous work indicated that transforming growth factor-beta (TGF-beta) elicits proliferation-inhibitory effects in the human colon carcinoma cell line MOSER. This paper describes the isolation and characterization of spontaneously arising subclones from this TGF-beta-sensitive parental line which were relatively refractory to the inhibitory effects of TGF-beta. While the parental cell line responded to TGF-beta with an inhibition of cellular proliferation in monolayer culture and in soft agarose, an increase in extracellular fibronectin, and a down-regulation of c-myc protooncogene expression, these responses were absent or attenuated in the sublines. However, the resistant clones retained the ability to specifically bind TGF-beta. N,N-Dimethylformamide and retinoic acid, two other agents associated with induction of a partial differentiation-like response in the MOSER parental cells (similar to that elicited by TGF-beta), inhibited the monolayer proliferation of both the parental cells and the TGF-beta-resistant sublines. Thus, the refractoriness observed in the isolated clones was relatively specific for TGF-beta.
Mulder
K M
KM
Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
Ramey
M K
MK
Hoosein
N M
NM
Levine
A E
AE
Hinshaw
X H
XH
Brattain
D E
DE
Brattain
M G
MG
D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004126:Dimethylformamide / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D009857:Oncogenes; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology
D014212:Tretinoin; D015291:Transforming Growth Factors; D004126:Dimethylformamide