ONCOGENE EXPRESSION IS MODULATED BY RECOMBINANT HUMAN INTERFERON-BETAIN HUMAN BREAST-CANCER CELLS

The effect of recombinant human interferon-beta on growth and oncoprot ein expression was investigated in several human breast-cancer cell li nes with different characteristics. All cell lines tested were sensiti ve to the antiproliferative action of the drug, regardless of their es trogen sensitivity. The maximal inhibition of cell proliferation was s een after 6 days of treatment. In estrogen-sensitive CG-5 and ZR-75-1 cells, but not in MDA-MB-453 estrogen-insensitive cells, a reduction i n c-myc and c-erbB2 oncoproteins occurred after 48-72 hr and became mo re pronounced after 120-168 hr of treatment, suggesting that this down -regulation is not direct but is mediated by undefined molecular mecha nisms. The time-course of the IFN-mediated decrease in oncoproteins se ems to indicate that this event is not strictly related to the IFN-reg ulation of cell proliferation. The expression of c-erbB2 and c-myc was also analyzed, after recombinant human interferon-p treatment, at the mRNA level in CG-5 cells. Surprisingly, no statistically significant variation of c-erbB2 or of c-myc mRNA was found either before or after 120-168 hr. Thus, we surmise that the observed reduction of oncoprote ins may be due to posttranscriptional mechanisms. (C) 1996 Wiley-Liss, Inc.