Rapid induction of PC3/BTG2 gene by hepatopoietin or partial hepatectomy and its mRNA expression in hepatocellular carcinoma.
BACKGROUND
The anti-proliferative gene, PC3 (pheoch-romocytoma cell 3)/BTG2 (B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family. This study aimed to assess the effects of recombinant human hepatopoietin (HPO) and partial hepatectomy on rapidly induced expression of immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in hepatocellular carcinoma (HCC) at different stages of progression.


METHODS
After a rat model of partial hepatectomy was established, we investigated gene expression within 1 hour after 2/3 partial hepatectomy by representational difference analysis and in a primary cultured hepatocyte system. The expression levels of PC3/BTG2 from liver tissues of the rat model were assessed by RT-PCR and Northern blotting. Meanwhile, the expression of BTG2 mRNA in a tissue microarray of HCC was determined by in situ hybridization.


RESULTS
The PC3/BTG2 gene was rapidly induced after 2/3 partial hepatectomy and its expression peaked within 1-2 hours after operation. HPO rapidly induced the expression of the genes c-fos, LRF-1, and PC3 in primary cultured rat hepatocytes, which might be one of the molecular mechanisms by which HPO stimulates hepatocyte proliferation. Positive BTG2 mRNA expression was detected in 71.19% (42/59) of the HCC samples and in 75% (3/4) of the normal liver tissue samples obtained from the region around the HCC tissues. PC3/BTG2 mRNA was located mainly in the cytoplasm of HCC cells and its expression was related to the degree of differentiation.


CONCLUSIONS
Recombinant human HPO and partial hepatectomy rapidly induce the expression of the PC3/BTG2 gene. PC3/BTG2 mRNA is highly expressed in HCC cells and its expression is related to the degree of cell differentiation. The abnormal expression of PC3/BTG2 is closely related to the genesis and development of HCC, so PC3/BTG2 may play an important role in these processes.
Zhang
Zhi-Min
ZM
Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Wang
Ge
G
Chen
Chuan
C
Yang
Zhi-Xiang
ZX
Jin
Feng
F
San
Jin-Lu
JL
Xu
Wen
W
Li
Qiong
Q
Li
Zeng-Peng
ZP
Wang
Dong
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D006498:Hepatectomy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000302:isolation & purification; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins
C521959:BTG2 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D017228:Hepatocyte Growth Factor