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Effects of Human Recombinant ₂ arg-Interferon and -Interferon on Human Breast Cancer Cell Lines: Dissociation of Antiproliferative Activity and Induction of HLA-DR Antigen Expression¹

Departments of Internal Medicine [G. G., E. L., C. G., C. H.] and Obstetrics and Gynecology, [C. M., I. M., G. D.], University Hospital, A-6020 Innsbruck, Austria, and E. Böhringer Institut für Arzneimittelforschung, Vienna, Austria [R. F.]

Human recombinant -interferon (rhu-IFN-) and human recombinant -interferon (rhu-IFN-₂ arg) with a chemical purity of over 95% were compared for their antiproliferative and HLA-DR-inducing activity in five human breast cancer cell lines (BT 20, ZR 75.1, MCF 7, 734B, Hs578T). Cytostatic effects on tumor cells were evaluated in monolayer cultures. HLA-DR antigen expression was examined by an indirect immunofluorescence technique using two different anti-HLA-DR monoclonal antibodies (anti-HLA-DR, VID-1) against framework determinants. rhu-IFN- and rhu-IFN-₂ arg differed in their antiproliferative efficiency in terms of both dose dependency and the spectrum of sensitive target cells. Combinations of rhu-IFN- and rhu-IFN-₂ always resulted in higher cytostatic effects. HLA-DR expression was exclusively inducible by rhu-IFN- and did not correspond to its antiproliferative activity. Furthermore, HLA-DR expression did not depend on proliferation but did require intact RNA and protein syntheses as shown by inhibition with cycloheximide and actinomycin D. HLA-DR antigen expression in mammary cancer lines was dependent on time, dose, and the continued presence of rhu-IFN-. Thus, our data suggest that in particular combinations type I and type II interferons might be useful in the treatment of breast cancer because they provide effective cytostatic and cell membrane-modulating properties.

¹ This work was financially supported by the Austrian research funds "Zur Förderung der wissenschaftlichen Forschung," Project 5288.

² To whom requests for reprints should be addressed, at Clinical Immunobiology, University Hospital, A-6020 Innsbruck, Austria.

Received 11/ 6/84. Revised 3/19/85. Accepted 3/25/85.

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