Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines.
Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.
Taylor
C W
CW
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Kim
Y S
YS
Childress-Fields
K E
KE
Yeoman
L C
LC
D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D004126:Dimethylformamide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002087:Butyrates; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D016211:Transforming Growth Factor alpha; D020148:Butyric Acid; D014212:Tretinoin; D004126:Dimethylformamide