Underexpression of mRNA in human hepatocellular carcinoma focusing on eight loci

Abstract

Genetic alterations associated with human hepatocellular carcinoma (HCC) have been reported previously, but are not sufficient to specify differences of HCCs from precancerous diseases of the liver, such as hepatitis, hepatic fibrosis, and cirrhosis. In the present study, we performed differential gene display analysis (DGDA) to clarify the specific genetic alterations associated with gene expression changes in the course of development of HCC from chronic viral hepatitis. Four pairs of surgically resected HCCs and hepatitis tissues were investigated. We found 1,028 expression sequence tags (ESTs) that were decreased or increased in HCC tissues compared with hepatitis tissues in the same patient. Nucleotide sequencing showed that they included 55 EST clones in the GenBank database, which were considered candidates for specific messenger RNA ( The following genetic alterations associated with human HCC have been reported: gene amplification of c-myc 4,5 in 33.3% to 36.4% of cases, point-mutations of K-ras 6,7 in 0 to 16.7% of cases and of p53 [8][9][10][11][12] in 23.1% to 50% of cases, and loss of heterozygosity of Rb 13,14 in 42.9% to 43.1% of cases and of p53 9,10 in 50% to 52.9% of cases. These percentages of genetic alterations are, however, not sufficient to indicate the mechanism by which precancerous liver diseases transform to HCC. To determine genetic alterations specific to HCCs, we performed differential gene display analysis 15 (DGDA) to compare mRNA expressions in HCC and noncancerous hepatitis tissue in the same patients. Patients and MethodsWritten informed consent was obtained from all human subjects, and the protocol of the present study was approved by the local ethics committee.

The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1

“…34,35 A recent study has shown that CPS1 gene transcription is downregulated in liver cancer tissues. 36 However, the absence of CPS1 in the cancer cell lines cannot be explained entirely by the hepatocellular differentiation state. It is known that all three cell lines express abundant levels of albumin and a-1 antitrypsin, indicating that many liver-specific transcription factors are present in these cell lines.…”

Decreased expression of cytochrome P450 2E1 is associated with poor prognosis of hepatocellular carcinoma

“…Several groups have independently suggested that CYP2E1 mRNA is down regulated in tumor tissues 26 and is differentially expressed in different liver tissues. 27 To our knowledge, our study is the first combined study to investigate the expression of CYP2E1 at both mRNA and protein levels in relation to HCC.…”

Molecular Determinants in the Transport of a Bile Acid-Derived Diagnostic Agent in Tumoral and Nontumoral Cell Lines of Human Liver

“…OATP1B1 has been reported to be down-regulated during neoplastic transformation in the liver (Kinoshita and Miyata, 2002). It was also shown that OATP1B1 and OATP1B3 are not detectable in HepG2 cells, widely used as a model of human hepatic carcinoma (Cui et al, 2003).…”