TGF-beta is an important factor in the regulation of liver growth. It is an
inhibitor of hepatocyte DNA synthesis and may induce active cell death, e.
g., to remove excessive tissue mass. Studies using transgenic mice suggest
that expression in the resting liver has to be well balanced; either under-
or overexpression appear to cause an increased turnover of hepatocytes and
to predispose to hepatocarcinogenesis. TGF-beta overexpression is frequent
ly observed in human hepatocellular carcinomas, probably as a late event in
tumor development. In men and mice, TGF-beta overexpression appears to be
associated with loss of TGF-beta responsiveness often by disruption of TGF-
beta signaling. However, mechanisms as mutations in TGF-beta receptor II or
Smad2 and 4 genes, frequently observed in other human cancers, have only r
arely been observed in hepatocellular carcinomas. Further studies may clari
fy the mechanisms by which hepatocellular tumors escape TGF-beta growth con
trol, as well as analyze possible roles of TGF-beta overexpression in immun
osuppression and angiogenesis. Microsc. Res. Tech. 52:430-436, 2001. (C) 20
01 Wiley-Liss, Inc.