1887

Abstract

Hepatitis B virus (HBV) X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) by activation of signalling pathways such as NF-B. To identify NF-B target genes differentially expressed in HBxAg-positive compared to -negative cells, HepG2 cells consistently expressing HBxAg (HepG2X cells) were stably transfected with pZeoSV2 or pZeoSV2-IB. mRNA from each culture was isolated and compared by PCR select cDNA subtraction. The results showed lower levels of -macroglobulin ( -M) in HepG2X-pZeoSV2 compared to HepG2X-pZeoSV2-IB cells. This was confirmed by Northern and Western blotting, and by measurement of extracellular -M levels. Elevated transforming growth factor-1 (TGF-1) levels were also seen in HepG2X compared to control cells. Serum-free conditioned medium (SFCM) from HepG2X cells suppressed DNA synthesis in a TGF--sensitive cell line, Mv1Lu. The latter was reversed when the SFCM was pretreated with exogenous, activated -M or with anti-TGF-. Since elevated TGF-1 promotes the development of many tumour types, these observations suggest that the HBxAg-mediated alteration in TGF-1 and -M production may contribute importantly to the pathogenesis of HCC.

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2004-02-01
2021-01-24
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