Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method

Dong, Xiao-yuan; Pang, Xuewen; Yu, Songtao; Su, Yan-Rong; Wang, Hongchen; Yin, Yuqin; Wang, Yuedan; Chen, Weifeng

doi:10.1002/ijc.20363

Cited by 53 publications

(35 citation statements)

References 31 publications

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“…[15][16][17] Interestingly, we also isolated a 196-bp cDNA fragment that was identical to a partial sequence of exon 3 of a known placenta-specific gene, PLAC1 (PLACenta-specific 1) (Fig. 1).…”

Section: Isolation Of Plac1 Gene Fragment In Hcc By Sshmentioning

confidence: 99%

Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients

Dong

Peng

et al. 2008

Intl Journal of Cancer

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Immunoselection and tumor evasion constitutes one of the major obstacles in cancer immunotherapy. A potential solution to this problem is the development of polyvalent vaccines, and the identification of more tumor-specific antigens is a prerequisite for the development of cancer vaccines. To identify novel tumor-specific antigens, suppression subtractive hybridization (SSH) was performed to isolate genes differentially expressed in human hepatocellular cancer (HCC) tissues. PLAC1 (PLACenta-specific 1) was one of the genes identified highly expressed in HCC tissues but not in paired noncancerous tissues. Further analyses revealed its expression in several other types of cancer tissues as well as tumor cell lines, but not in normal tissues except for placenta. Among HCC samples tested, 32% (22/69) showed PLAC1 mRNA expression while the protein was detected in 23.3% (7/30). A serological survey revealed that 3.8% (4/101) of HCC patients had anti-PLAC1 antibody response, suggesting the immunogenicity of PLAC1 in HCC patients. PLAC1 represents a new class of tumor associated antigen with restricted expression in placenta and cancer tissues, that may serve as a target for cancer vaccination.

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Section: Isolation Of Plac1 Gene Fragment In Hcc By Sshmentioning

confidence: 99%

Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients

Dong

Peng

et al. 2008

Intl Journal of Cancer

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“…been reported as a novel protein that is secreted from the liver, white adipose tissue (WAT) and brown adipose tissue (BAT) and proliferates mouse β-cells [3][4][5][6][7]. However, ANGPTLl8-/-mice revealed no abnormalities in glucose homeostasis and entirely normal β-cell expansion [8].…”

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Betatrophin expression is promoted in obese hyperinsulinemic type 2 but not type 1 diabetic mice

Nakata

Shinozaki

et al. 2016

Endocr J

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“…Hepatoma cell lines and hepatocellular carcinomas (HCC) 3 undergo phenotypic dedifferentiation leading to the loss or low expression of typical hepatic functions such as plasma protein synthesis or xenobiotic detoxification (1)(2)(3). Dedifferentiation is a key early event in the pathogenesis of HCC that has been associated with an altered expression of liver-enriched transcription factors (4,5).…”

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confidence: 99%

Underexpressed Coactivators PGC1α AND SRC1 Impair Hepatocyte Nuclear Factor 4α Function and Promote Dedifferentiation in Human Hepatoma Cells

Martínez-Jiménez

Gómez-Lechón

Castell

et al. 2006

Journal of Biological Chemistry

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Hepatocyte nuclear factor 4␣ (HNF4␣) plays critical roles during liver development and in the transcriptional regulation of many hepatic genes in adult liver. Here we have demonstrated that in human hepatoma HepG2 cells, HNF4␣ is expressed at levels as high as in human liver but its activity on target genes is very low or absent. We have discovered that the low expression of key coactivators (PGC1␣, SRC1, SRC2, and PCAF) might account for the lack of function of HNF4␣ in HepG2 cells. Among them, PGC1␣ and SRC1 are the two most important HNF4␣ coactivators as revealed by reporter assays with an Apo-CIII promoter construct. Moreover, the expression of these two coactivators was found to be down-regulated in all human hepatomas investigated. Overexpression of SRC1 and PGC1␣ by recombinant adenoviruses led to a significant up-regulation of well characterized HNF4␣-dependent genes (ApoCIII, ApoAV, PEPCK, AldoB, OTC, and CYP7A1) and forced HepG2 cells toward a more differentiated phenotype as demonstrated by increased ureogenic rate. The positive effect of PGC1␣ was seen to be dependent on HNF4␣. Finally, insulin treatment of human hepatocytes and HepG2 cells caused repression of PGC1␣ and a concomitant down-regulation of ApoCIII, PEPCK, AldoB, and OTC. Altogether, our results suggest that SRC1, and notably PGC1␣, are key coactivators for the proper function of HNF4␣ in human liver and for an integrative control of multiple hepatic genes involved in metabolism and homeostasis. The down-regulation of key HNF4␣ coactivators could be a determinant factor for the dedifferentiation of human hepatomas. Hepatoma cell lines and hepatocellular carcinomas (HCC)3 undergo phenotypic dedifferentiation leading to the loss or low expression of typical hepatic functions such as plasma protein synthesis or xenobiotic detoxification (1-3). Dedifferentiation is a key early event in the pathogenesis of HCC that has been associated with an altered expression of liver-enriched transcription factors (4, 5). Similarly, studies in hepatoma cell lines have revealed that the maintenance of a differentiated hepatic phenotype is dependent on the expression of liver-enriched transcription factor (6, 7).Current research supports the notion that hepatocyte nuclear factor 4␣ (HNF4␣) is one of the most important liverenriched transcription factors for hepatocyte differentiation. HNF4␣ is a highly conserved member of the nuclear receptor superfamily that was initially identified as a factor required for liver-specific gene expression (8). HNF4␣ plays critical roles not only in the specification of the hepatic phenotype during liver development but also in the transcriptional regulation of genes involved in glucose, cholesterol, fatty acids, and xenobiotic metabolism and in the synthesis of blood coagulation factors (9 -12). Disruption of HNF4␣ leads to an early embryonic lethal phenotype associated with a failure of differentiation of visceral endoderm (13). Genome-scale location analysis revealed surprising results for HNF4␣ in hepatocytes. The number...

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Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method

Abstract: To identify differentially expressed genes in human HCC in China, we applied a modified SSH method for cDNA subtraction. Such modification has made the method more effective for subtraction.

Cited by 53 publications

References 31 publications

Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients

Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients

Betatrophin expression is promoted in obese hyperinsulinemic type 2 but not type 1 diabetic mice

Underexpressed Coactivators PGC1α AND SRC1 Impair Hepatocyte Nuclear Factor 4α Function and Promote Dedifferentiation in Human Hepatoma Cells

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