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[Cancer Research 61, 2809-2812, April 1, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

A Light, Nontoxic Interleukin 12 Protocol Inhibits HER-2/neu Mammary Carcinogenesis in BALB/c Transgenic Mice with Established Hyperplasia1

Loredana Cifaldi, Elena Quaglino, Emma Di Carlo, Piero Musiani, Michela Spadaro, Pier Luigi Lollini, Stanley Wolf, Katia Boggio, Guido Forni and Federica Cavallo2

Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy [L. C., E. Q., M. S., K. B., G. F., F. C.]; Department of Oncology and Neurosciences, G. d’Annunzio University, 66013 Chieti, Italy [E. D. C., P. M.]; Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy [P. L. L.]; and Genetics Institute, Cambridge, Massachusetts 02140 [S. W.]

With a slight asynchronous but consistent progression, all of the mammary glands of female BALB/c mice transgenic for the transforming rat HER-2/neu oncogene progress to atypical hyperplasia and to invasive carcinoma. Previous studies have shown that chronic administration of interleukin (IL) 12 started at the 2nd week of age hampers this progression because of its ability to inhibit tumor angiogenesis and activate a nonspecific immune response. Here we show that a similar inhibition is achieved when 7-week-old mice with fully blown atypical hyperplasia receive a weekly injection of 100 ng IL-12 for 16 times. This lower-dose and later IL-12 administration induces high and sustained levels of serum IFN-{gamma} equivalent to those elicited by more frequent administrations. A lower-dose and less toxic treatment may thus be envisaged as a possible option in the management of preneoplastic mammary lesions.




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