Human homologue of maid is a useful marker protein in hepatocarcinogenesis
| Autor: | Snorri S. Thorgeirsson, Isao Sakaida, Haruko Tanimoto, Takahiro Yamasaki, Taro Takami, Shuji Terai, Yuichiro Yokoyama, Koichi Uchida, Kiwamu Okita, Hiroshi Nishina, Kunihiko Tajima |
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| Rok vydání: | 2005 |
| Předmět: |
Adenoma
Male Immunoprecipitation Biology chemistry.chemical_compound RNA interference Two-Hybrid System Techniques medicine Biomarkers Tumor Animals Humans DAPI Rats Wistar Hepatology Cell growth COP9 Signalosome Complex Helix-Loop-Helix Motifs Liver Neoplasms Gastroenterology Intracellular Signaling Peptides and Proteins RNA medicine.disease Molecular biology Rats DNA-Binding Proteins Hepatocyte nuclear factor 4 chemistry Hepatocellular carcinoma Immunohistochemistry RNA Interference Precancerous Conditions Cell Division Peptide Hydrolases Transcription Factors |
| Zdroj: | Gastroenterology. 128(5) |
| ISSN: | 0016-5085 |
| Popis: | Background & Aims: Human homologue of maid (HHM) is a helix-loop-helix (HLH) transcriptional regulatory protein that is involved in the hepatic stem cell development and differentiation. We analyzed the potential involvement of HHM in hepatocarcinogenesis. Methods: We analyzed HHM expression in the choline-deficient L-amino acid defined (CDAA) diet model of rat hepatocarcinogenesis and in human adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC) biopsy samples. We assessed the effects of HHM on cell proliferation. We screened proteins that bind to HHM protein using a yeast 2-hybrid screen. Results: High HHM expression was seen in foci and HCC induced in the rat CDAA diet model. HHM protein was expressed in 23 of 32 AH samples (72%), 19 of 28 well-differentiated HCC samples (68%), and 9 of 18 poorly-moderately differentiated HCC samples (50%). Over-expressed HHM enhanced the S phase. HHM interference RNA significantly inhibited cell proliferation. A yeast 2-hybrid screen identified Jun activation domain-binding protein 1 (Jab1) as a binding partner for HHM. We confirmed HHM and Jab1 binding by immunoprecipitation and immunofluorescent histochemistry. The expression of Jab1 was found in human AH and HCC samples. We found an association between levels of expression of HHM and those of Jab1 in AH and HCC tissues examined ( P = .027 by χ 2 test). Conclusions: High-level HHM expression was found from the very early stages of hepatocarcinogenesis, suggesting that HHM may be a useful marker protein to detect. |
| Databáze: | OpenAIRE |
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