NEU AND RAS INITIATE MURINE MAMMARY-TUMORS THAT SHARE GENETIC-MARKERSGENERALLY ABSENT IN C-MYC AND INT-2-INITIATED TUMORS

We have previously shown that each of four activated oncogenes (c-myc, nea, ras, and int-2) can serve as transgenic initiators of morphologi cally distinct adenocarcinomas of the murine mammary gland. Since abno rmalities of these oncogenes are found frequently in human breast canc ers, such differences are of particular interest. Thus, the distinctiv eness of each murine tumor type might reflect a relationship between a specific oncogene and a susceptible target cell or might reflect dist inctive changes brought about by the idiosyncratic action of each onco gene. We have identified six genes (two of them novel) expressed in tu mors initiated by nea, but usually absent from tumors initiated by c-m yc. The expression of these genes (kappa-casein, transferrin, cellular retinol binding protein I (CRBPI), WDNM1, and the two novel ones) can not be induced in c-myc-initiated tumors by the introduction of an act ivated nea oncogene nor can their expression be inhibited in nea-initi ated tumors by the introduction of c-myc. Therefore, these genes appea r to represent markers of a cell type preferentially transformed by ne u. Further analysis reveals that the six markers are also expressed by ras-initiated mammary tumors, but not by int-2 initiated tumors sugge sting that neu/ras-initiated tumors share a common cellular lineage an d/or a common signal transduction pathway. Interestingly, one of the n ovel marker genes (Mat-8) appears to encode a cell-surface chloride ch annel and the other, a secreted protein with homologies to glycosyl hy drolases, both of which might be useful for the diagnosis and treatmen t of specific mammary tumors.