Expression of estrogen receptors (ER)-α and -β, as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER-α and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER-α variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-β was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-α variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER-α variant (vER-α) is not related to male HCC prevalence. In addition, the predominant expression of ER-β in HCV patients suggests that it plays an important role in HCV-induced liver disease.

Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of target genes involved in crucial aspects of cancer development. This study investigated the expression of HIFs and their contribution to the regulation of target genes related to angiogenesis and glucose metabolism in gastric cancer. The data showed that HIFs were over-expressed in gastric cancer and that activation of the target genes was observed mainly in the early stages. Moreover, the results of the present study revealed that only HIF-1α, but not HIF-2α dimerizes with HIF-1β and then regulates expression of target genes in response to hypoxia. The results of the present study demonstrate that HIF-1α and HIF-1β enhances expression of VEGF and glucose metabolism-related genes in response to hypoxia in gastric cancer. These data offer important information regarding HIF pathways in the development of gastric cancer.

Chromatin structure has a central role in the regulation of gene expression, 1) and several mechanisms play important roles in chromatin remodeling events by the modification of histone amino-termini that extend from the core particles of chromatin. Among these functions, histone acetylation is particularly important because gene activity was first correlated with this event.2) The status of histone acetylation is controlled by the competition between two classes of enzymes, histone deacetyltransferases (HDACs) and histone acetyltransferases (HATs).3) These enzymes participate in a variety of cellular processes including transcription, DNA replication, and cell cycle progression. Owing to their important roles in the regulation of these events, it has been suggested that the enzymes that affect the status of histone acetylation are associated with proliferative diseases such as tumors. 4) In fact, HDAC has recently attracted interest as a novel anti-tumor therapeutic target. HDAC inhibitors (HDACi) have been shown to induce growth arrest, differentiation, and apoptosis of cancer cells in vitro and in vivo. 5)The class I enzyme HDAC1 was the first mammalian deacetylase identified. 6) Numerous transcription factors, including regulators of the cell cycle, differentiation, and development, have been shown to associate with HDAC1, thereby mediating the repression of specific target genes. [7][8][9] The disruption of both HDAC1 alleles results in embryonic lethality as a result of severe proliferation defects and retardation in development.10) Moreover, the loss of HDAC1 leads to significantly reduced overall deacetylase activity, and no alternate pathway replaces it.10) On the other hand, several types of human cancer are known to have higher HDAC1 activities than normal cells.11) MS-27-275, a new HDACi that preferentially inhibits HDAC1, was recently identified. 12)Along with TSA, MS-27-275 increased histone H4 acetylation and induced apoptosis in the human colon cancer cell line SW620. Collectively, these findings indicate that HDAC1 has important roles in development and proliferative diseases such as cancer and that it is not replaced by an alternate enzyme.We have reported on transgenic mice that over-expressed human HDAC1 in many tissues. However, the pathological changes, including steatosis and nuclear pleomorphism, were specifically found in liver tissues.13) To find out if the overactivation of HDAC1 was a potential factor contributing to the cellular pathological changes through the regulation of the related genes, the expression profiles of the genes related to the cell cycle, apoptosis, and lipid metabolism were determined in this study. METHODS AND MATERIALS Experimental AnimalsWe previously reported on transgenic mice that expressed the human HDAC1 gene in many tissues.13) However, significant pathological changes were only detected in the hepatic tissue of the transgenic mice compared with that of the control littermates. To determine if the over-expression of HDAC1 contributes to gene expression, wh...

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