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TGFβ gene transcription in normal and neoplastic liver growth
Author(s) -
Carr Brian I.,
Huang Ting H.,
Itakura Keiichi,
Noël Micheline,
Marceau Normand
Publication year - 1989
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240390413
Subject(s) - biology , paracrine signalling , cell culture , gene expression , hep g2 , liver cell , microbiology and biotechnology , population , gene , carcinogen , autocrine signalling , transforming growth factor , messenger rna , endocrinology , medicine , biochemistry , genetics , receptor , environmental health
TGFβ is a potent, nontoxic inhibitor of mitogen‐induced DNA synthesis in primary cultures of adult rat hepatocytes. Using a cDNA probe, we investigated TGFβ gene expression in quiescent, regenerating, and neoplastic liver, and several hepatoma lines by Northern gel analysis. We found that regenerating liver had increased TGFβ gene transcripts beginning at about 8 h, with a broad peak of 48–120 h and return to normal after 9 days. Separation of the regenerating liver into its constituent cell types, followed by RNA extraction and reprobing, revealed that increased TGFβ gene transcripts were confined to the enriched endothelial‐cell population and not the hepatocytes. Increased hepatic TGFβ expression was also found in fetal liver and in rats immediately after birth. Elevated TGFβ mRNA levels were also found in primary cultures of oval cells and an established bile ductular cell line, as well as in carcinogen‐altered liver epithelial cell lines. Transcripts were undetectable in normal human liver but were abundant in the human hepatoma lines Hep G2, Hep 3B, PLC/PRF/5, and SK‐Hep‐1. Elevated levels were also found in the normal rat liver–derived lines BRL‐3A and clone 9 and the H4IIE rat hepatoma, but not in the HTC, MH 1 C 1 , and MH7777 rat hepatomas. The hepatocarcinogen diethylnitrosamine induced high transcript levels after single injections in a time‐ and dose‐dependent manner. These results suggest that the liver may be a paracrine organ with respect to TGFβ gene expression, which can be induced by carcinogens and by growth stimulation.