Initiating oncogenic event determines gene-expression patterns of human breast cancer models.
Molecular expression profiling of tumors initiated by transgenic overexpression of c-myc, c-neu, c-ha-ras, polyoma middle T antigen (PyMT) or simian virus 40 T/t antigen (T-ag) targeted to the mouse mammary gland have identified both common and oncogene-specific events associated with tumor formation and progression. The tumors shared great similarities in their gene-expression profiles as compared with the normal mammary gland with an induction of cell-cycle regulators, metabolic regulators, zinc finger proteins, and protein tyrosine phosphatases, along with the suppression of some protein tyrosine kinases. Selection and hierarchical clustering of the most variant genes, however, resulted in separating the mouse models into three groups with distinct oncogene-specific patterns of gene expression. Such an identification of targets specified by particular oncogenes may facilitate development of lesion-specific therapeutics and preclinical testing. Moreover, similarities in gene expression between human breast cancers and the mouse models have been identified, thus providing an important component for the validation of transgenic mammary cancer models.
Desai
Kartiki V
KV
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA.
Xiao
Nianqing
N
Wang
Weili
W
Gangi
Lisa
L
Greene
John
J
Powell
John I
JI
Dickson
Robert
R
Furth
Priscilla
P
Hunter
Kent
K
Kucherlapati
Raju
R
Simon
Richard
R
Liu
Edison T
ET
Green
Jeffrey E
JE
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D018734:Genes, erbB-2; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011519:Proto-Oncogenes
D000952:Antigens, Polyomavirus Transforming