IDENTIFICATION OF A NEW INTERFERON-ALPHA-INDUCIBLE GENE-(P27) ON HUMAN CHROMOSOME-14Q32 AND ITS EXPRESSION IN BREAST-CARCINOMA

A new complementary DNA, p27, has been cloned and sequenced from estra diol-treated MCF7 human breast carcinoma cells. It encodes a putative highly hydrophobic protein of 122 amino acids which has a 33% overall sequence similarity to the product of the 6-16 gene (R. L. Friedman, S . P. Manly, M. McMahon, I. M. Kerr, and G. R. Stark, Cell, 38: 745-755 , 1984), which is transcriptionally induced by interferons of the alph a/beta type. We demonstrate here that the p27 gene, which is located i n band q32 of human chromosome 14, is also induced by interferon-alpha in human cell lines of different origin and that expression is indepe ndent of the presence of estradiol receptor in the cells. High levels of p27 RNA were found in vivo in approximately 50% of primary human br east carcinomas (21 were tested by Northern blotting). In situ hybridi zation to some of the p27-overexpressing tumors showed that the p27 RN A is localized in cancer cells and sometimes also in fibroblastic cell s of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estro gen-induced pS2 gene. Further studies are now necessary to elucidate t he cause of p27 gene overexpression in breast carcinoma and in particu lar to determine whether it corresponds to chromosomal rearrangements in the 14q32 region and/or to induction by interferons of the alpha/be ta type.