Gene expression of ABC proteins in hepatocellular carcinoma, perineoplastic tissue, and liver diseases.
BACKGROUND
The development of hepatocellular carcinoma (HCC) is a frequent event during the natural history of cirrhosis. Effective treatment is, however, hampered by drug resistance related to the expression of multidrug resistance (MDR) proteins belonging to the ABC family transporters. Studying expression of genes coding for these proteins may help to explain the potential sensitivity of HCC to chemotherapy.


METHODS
The expression of MRP1, MRP2, MRP3, MDR1, and MDR3 was investigated by quantitative RT-PCR analyses in paraffin-embedded tissues obtained from 9 cases of HCC, 16 cases of cirrhosis, 10 cases of chronic extrahepatic cholestasis, and 16 cases of normal liver. In HCC cases, gene expression was assessed both in neoplastic and perineoplastic tissue after microscopically assisted microdissection.


RESULTS
MRP1 was significantly and similarly overexpressed in HCC and perineoplastic tissue. MRP2 and MDR1 were also increased in HCC, but the level of expression did not correlate with that of perineoplastic tissue. The level of expression was either reduced or normal in cirrhotic liver and during chronic cholestasis. Expression of MDR3 was unchanged in all conditions investigated.


CONCLUSIONS
The genetic expression of multi-drug resistance proteins, in particular MRP1, MRP2, and MDR1, is increased during HCC. In the case of MRP1, the extent of expression is similar in neoplastic and perineoplastic tissue, but this is not the case for MRP2 and MDR1. The assessment of ABC protein expression pattern may provide important information for the diagnosis and treatment of HCC.
Bonin
Serena
S
Department of Clinical, Morphological and Technological Sciences, University of Trieste, Italy.
Pascolo
Lorella
L
Crocé
Lory S
LS
Stanta
Giorgio
G
Tiribelli
Claudio
C
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger