The effects of continuous exposure to epidermal growth factor on the spontaneous transformation of cultured rat liver epithelial cells.
A long-term continuous exposure to epidermal growth factor (EGF) enhanced the tumorigenicity of spontaneously transformed cells arising in a clonal population of normal cultured rat liver epithelial cells propagated in a selective growth condition. Lengthy EGF exposure also induced the expression of several phenotypes that differed from the phenotypes of rat liver epithelial cells transformed spontaneously in the absence of EGF. Epidermal growth factor treatment caused consistently an enhancement of the constitutive mRNA expression of transforming growth factor-alpha (TGF-alpha), but not of the EGF receptor and transforming growth factor-beta. The overexpression of TGF-alpha persisted in cell lines derived from tumors formed by the EGF-treated transformed cells. These tumors also exhibited high metastatic incidence and ductal cell differentiation. In contrast, untreated spontaneously transformed cells formed non-metastatic tumors with hepatocellular differentiation. These results suggest that long-term, continuous exposure to EGF/TGF-alpha may modulate the phenotypic expressions of neoplastic transformation.
Tsao
M S
MS
Department of Pathology, Montreal General Hospital, Quebec, Canada.
Zhang
X Y
XY
D000818:Animals; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D008113:Liver Neoplasms / Q000737:chemistry / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)