Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Aberrant methylation of CpG islands within the promoter regions of tumor suppressor or cancer-related genes is a common mechanism leading to the silencing of gene expression. To determine whether aberrant methylation is a contributing factor to transcriptional inactivation of DLC-1 (
deleted in liver cancer-1
), a candidate tumor suppressor gene, we examined its methylation status in twelve
hepatocellular carcinoma
. breast, colon, and prostate tumor cell lines with low or undetectable expression of DLC-1. By Southern blot analysis of DNA digested with the methylation sensitive enzyme HpaII, we found a different degree of promoter hypermethylation in all cell lines with aberrant DLC-1 expression. The hypermethylation status was reversed by the addition of 5-aza-2'-deoxycytidine, a demethylating agent, in one human
hepatocellular carcinoma
line. These observations suggest that hypermethylation is responsible for abrogating the function of the DLC-1 gene in a subset of liver, breast, colon, and prostate cancers.
...
PMID:Promoter hypermethylation of DLC-1, a candidate tumor suppressor gene, in several common human cancers. 1264 48
The gene
deleted in liver cancer-1
(
DLC-1
) is located on human chromosome 8p21-22, a region thought to harbor tumor suppressor genes on the basis of its frequent deletion or loss of heterozygosity in a variety of human cancers, including
hepatocellular carcinoma
(
HCC
). Deletion or altered expression of
DLC-1
is common in
HCC
. In the current study, the subcellular localization of
Dlc-1
protein was determined by immunostaining with antibody to
DLC-1
and the possible tumor growth suppressor activity of
DLC-1
was investigated by examining the effects of of
DLC-1
cDNA transfection in two human
HCC
cell lines lacking expression of the endogenous gene. The results show that Dlc-1protein is localized in the cell cytoplasm, and the restoration of
DLC-1
expression in
HCC
cells resulted in caspase-3-mediated apoptosis, inhibition of cell growth and invasiveness in vitro as well as in reduction of the ability of the cells to form tumors in athymic nude mice. These observations thus support the notion that
Dlc-1
protein is involved in hepatocarcinogenesis and has oncosuppressive activity in
HCC
.
...
PMID:Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. 1464 17
DLC-1 (
deleted in liver cancer-1
) is a tumor suppressor gene for
hepatocellular carcinoma
and other cancers. To characterize its functions, we constructed recombinant adenovirus encoding the wild-type DLC-1 and examined its effects on behaviors of a
hepatocellular carcinoma
cell line (SNU-368), which does not express DLC-1. Here, we found that restoration of DLC-1 expression in the SNU-368 cells caused an inhibition of cell proliferation with an increase of a subG1 population. Furthermore, DLC-1 overexpression induced disassembly of stress fibers and extensive membrane protrusions around cells on laminin-1. DLC-1 overexpression also inhibited cell migration and dephosphorylated focal adhesion proteins such as focal adhesion kinase (FAK), Cas (p130Cas; Crk-associated substrate), and paxillin. These observations suggest that DLC-1 plays important roles in signal transduction pathway regulating cell proliferation, cell morphology, and cell migration by affecting Rho family GTPases and focal adhesion proteins.
...
PMID:DLC-1, a GTPase-activating protein for Rho, is associated with cell proliferation, morphology, and migration in human hepatocellular carcinoma. 1729 27
