Up-regulation of transforming growth factor alpha expression by transforming growth factor beta 1, epidermal growth factor, and N,N-dimethylformamide in human colon carcinoma cells.
This report examines the effects of inhibitors of cell proliferation on transforming growth factor alpha (TGF-alpha) expression in low-density cultures of poorly (PD) and well-differentiated (WD) human colon carcinoma cells, continuously maintained in serum-free medium. In contrast to results in certain untransformed cells, growth inhibitors such as transforming growth factor beta 1 (TGF-beta 1) and N,N-dimethylformamide up-regulated TGF-alpha mRNA and protein expression in these human colon carcinoma cells. Treatment of low-density WD cells with TGF-beta 1 (10 ng/ml) resulted in a 1.5-fold increase in TGF-alpha mRNA levels within 4 h of treatment. TGF-alpha mRNA levels increased to 2.7-fold above control values by 48 h after TGF-beta 1 addition. Additionally, over a TGF-beta 1 concentration range of 1-30 ng/ml, TGF-alpha protein levels were increased by 2-10-fold, despite the fact that the growth of the WD cells remained inhibited. Although TGF-beta 1 control of TGF-alpha expression was altered in these WD colon carcinoma cells, relative to that in untransformed cells previously examined, the cells retained the ability to up-regulate TGF-alpha expression in an epidermal growth factor-dependent manner. In similarity to the results with TGF-beta 1 in WD colon carcinoma cells, the differentiation agent N,N-dimethylformamide (0.7%) resulted in an increase of TGF-alpha mRNA of approximately 3.8-fold in PD colon carcinoma cells, as well as a 4.4-fold increase in TGF-alpha protein after 4 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033.
P A
PA
Zipfel
B L
BL
Ziober
S L
SL
Morris
K M
KM
Mulder
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D004126:Dimethylformamide / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D004126:Dimethylformamide