Unknown

Dataset Information

0

Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation.


ABSTRACT: Hepatocellular carcinoma (HCC) has the most rapidly rising cancer incidence in the US and Europe. The KLF6 tumor suppressor is frequently inactivated in HCC by loss-of-heterozygosity (LOH) and/or mutation.Here we have analyzed 33 HBV- and 40 HCV-related HCCs for mRNA expression of wildtype KLF6 (wtKLF6) as well as the KLF6 variant 1 (SV1), a truncated, growth-promoting variant that antagonizes wtKLF6 function. The HCV-related tumors analyzed represented the full histologic spectrum from cirrhosis and dysplasia to metastatic cancer.Expression of KLF6 mRNA is decreased in 73% of HBV-associated HCCs compared to matched surrounding tissue (ST), with reductions of approximately 80% in one-third of the patients. KLF6 mRNA expression is also reduced in dysplastic nodules from patients with HCV compared to cirrhotic livers (p<0.005), with an additional, marked decrease in the very advanced, metastatic stage (p<0.05). An increased ratio of KLF6SV1/wt KLF6 is present in a subset (6/33, 18%) of the HBV-related HCCs compared to matched ST. Reconstituting KLF6 in HepG2 cells by retroviral infection decreased proliferation and related markers including cyclin D1 and beta-catenin, increased cellular differentiation based on induction of albumin, E-cadherin, and decreased alpha fetoprotein.We conclude that reduced KLF6 expression is common in both HBV- and HCV-related HCCs and occurs at critical stages during cancer progression. Effects of KLF6 are attributable to regulation of genes controlling hepatocyte growth and differentiation.

SUBMITTER: Kremer-Tal S 

PROVIDER: S-EPMC3533246 | BioStudies | 2007-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3412196 | BioStudies
2008-01-01 | S-EPMC2600656 | BioStudies
2010-07-06 | E-GEOD-19665 | ArrayExpress
2010-07-06 | GSE19665 | GEO
2011-01-01 | S-EPMC3144998 | BioStudies
2019-01-01 | S-EPMC6923823 | BioStudies
2016-01-01 | S-EPMC5342339 | BioStudies
1000-01-01 | S-EPMC3926946 | BioStudies
2019-01-01 | S-EPMC6337822 | BioStudies
1000-01-01 | S-EPMC4179959 | BioStudies