Antisense of ATP synthase subunit e inhibits the growth of human hepatocellular carcinoma cells.

Differentially expressed genes between normal and hepatocellular carcinoma tissues were investigated using differential display. We identified a cDNA fragment that was overexpressed in cancer tissue. Homology analysis showed that the sequence was identical to human ATP synthase subunit e (hAS-e). Moreover, Northern blot analysis demonstrated that hAS-e was overexpressed in 10 of 11 (91%) specimens of hepatocellular carcinoma compared with corresponding normal tissues. We introduced antisense hAS-e into a human hepatocellular carcinoma BEL-7404 cell and found that downregulation of the hAS-e led to cell growth inhibition. It was also found that the antisense transfection could decrease the serum-stimulated activation of mitogen-activated protein kinase (MAP kinase). Together, the results suggest that antisense of hAS-e can inhibit cell proliferation through the MAP kinase pathway. Our data indicate that hAS-e may become a new target in gene therapy.

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