Abstract
A new complementary DNA, p27, has been cloned and sequenced from estradiol-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 α/β type. We demonstrate here that the p27 gene, which is located in band q32 of human chromosome 14, is also induced by interferon-α in human cell lines of different origin and that expression is independent of the presence of estradiol receptor in the cells. High levels of p27 RNA were found in vivo in approximately 50% of primary human breast carcinomas (21 were tested by Northern blotting). In situ hybridization to some of the p27-overexpressing tumors showed that the p27 RNA is localized in cancer cells and sometimes also in fibroblastic cells of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estrogen-induced pS2 gene. Further studies are now necessary to elucidate the cause of p27 gene overexpression in breast carcinoma and in particular to determine whether it corresponds to chromosomal rearrangements in the 14q32 region and/or to induction by interferons of the α/β type.
Supported by funds from the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the Mutuelle Générale de l'Education Nationale, the Ministère de la Recherche et de l'Espace (contrat 92H.091), the Centre Hospitalier Universitaire Régional, the Association pour la Recherche sur le Cancer, the Ligue Nationale Française contre le Cancer, the Fondation pour la Recherche Médicale Française, the Groupement des Entreprises Françaises pour la Lutte contre le Cancer, and the Fondation Jeantet.