Human homologue of maid is a useful marker protein in hepatocarcinogenesis.
OBJECTIVE
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 chi2 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.
Takami
Taro
T
Department of Molecular Science and Applied Medicine (Gastroenterology and Hepatology), Yamaguchi University School of Medicine, Ube, Japan.
Terai
Shuji
S
Yokoyama
Yuichiro
Y
Tanimoto
Haruko
H
Tajima
Kunihiko
K
Uchida
Koichi
K
Yamasaki
Takahiro
T
Sakaida
Isao
I
Nishina
Hiroshi
H
Thorgeirsson
Snorri S
SS
Okita
Kiwamu
K
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor; D000075686:COP9 Signalosome Complex; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D014408:Biomarkers, Tumor; C485815:CCNDBP1 protein, human; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex