Bw. Morrison et P. Leder, NEU AND RAS INITIATE MURINE MAMMARY-TUMORS THAT SHARE GENETIC-MARKERSGENERALLY ABSENT IN C-MYC AND INT-2-INITIATED TUMORS, Oncogene, 9(12), 1994, pp. 3417-3426
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.