neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors.
We have previously shown that each of four activated oncogenes (c-myc, neu, ras, and int-2) can serve as transgenic initiators of morphologically distinct adenocarcinomas of the murine mammary gland. Since abnormalities of these oncogenes are found frequently in human breast cancers, such differences are of particular interest. Thus, the distinctiveness of each murine tumor type might reflect a relationship between a specific oncogene and a susceptible target cell or might reflect distinctive changes brought about by the idiosyncratic action of each oncogene. We have identified six genes (two of them novel) expressed in tumors initiated by neu, but usually absent from tumors initiated by c-myc. The expression of these genes (kappa-casein, transferrin, cellular retinol binding protein I (CRBPI), WDNM1, and the two novel ones) cannot be induced in c-myc-initiated tumors by the introduction of an activated neu oncogene nor can their expression be inhibited in neu-initiated tumors by the introduction of c-myc. Therefore, these genes appear to represent markers of a cell type preferentially transformed by neu. Further analysis reveals that the six markers are also expressed by ras-initiated mammary tumors, but not by int-2-initiated tumors suggesting that neu/ras-initiated tumors share a common cellular lineage and/or a common signal transduction pathway. Interestingly, one of the novel marker genes (Mat-8) appears to encode a cell-surface chloride channel and the other, a secreted protein with homologies to glycosyl hydrolases, both of which might be useful for the diagnosis and treatment of specific mammary tumors.
Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115.
B W
BW
Morrison
P
P
Leder
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004273:DNA, Neoplasm; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D016259:Genes, myc; D011905:Genes, ras; D005819:Genetic Markers; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017386:Sequence Homology, Amino Acid
D004273:DNA, Neoplasm; C489197:Fgf3 protein, mouse; C489199:Fgf3 protein, rat; D051518:Fibroblast Growth Factor 3; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors