Overexpression of the two nucleotide excision repair genes ERCC1 and XPC in human hepatocellular carcinoma.
OBJECTIVE
Little is known about the nucleotide excision repair (NER) pathway in the resistance of human hepatocellular carcinoma (HCC) to chemotherapeutics. We investigated expression of several NER genes in human HCC and matching non-tumor tissue (NT) and in normal liver.


METHODS
Expression of CSA, CSB, XPC, hHR23B, XPA, XPB, ERCC1 and p53 genes was analyzed by quantitative RT-PCR and immunoblotting in 26 HCC and 9 normal livers.


RESULTS
The seven NER genes and p53 were frequently overexpressed in HCC compared to matched NT. XPA, XPC, hHR23B and ERCC1 mRNA levels were significantly increased (p<0.05) in HCC arising in cirrhotic livers compared to non fibrotic tissue. Moreover, expression of ERCC1, XPA and XPC mRNA was significantly augmented in HCC, even more in tumors arising in cirrhotic liver. ERCC1, XPC ad XPA mRNA levels were highly correlated in NT and HCC. XPC and ERCC1 protein levels were also increased in HCC.


CONCLUSIONS
Our findings strongly suggest that overexpression of two key genes involved in the early steps of the NER process, ERCC1 and XPC, is associated with liver fibrogenesis and cancer and could be related to the well recognized resistance of HCC to chemotherapeutics.
Fautrel
Alain
A
INSERM U620, Détoxication et Reparation Tissulaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, 35043 Rennes Cedex, France.
Andrieux
Lise
L
Musso
Orlando
O
Boudjema
Karim
K
Guillouzo
André
A
Langouët
Sophie
S
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D012334:RNA, Neoplasm; C086984:XPC protein, human; C071447:ERCC1 protein, human; D004720:Endonucleases