Developmental timing of activated erbB2 expression plays a critical role in the induction of mammary tumors.
Mammary specific expression of the activated erbB2 in the mammary epithelium has been demonstrated to be a potent inducer of mammary carcinomas in number of different transgenic mouse models. Indeed we have recently shown that mammary epithelial specific activation of erbB2 under the transcriptional control of the endogenous erbB2 promoter is capable of inducing focal mammary tumors after a long latency period. To assess whether the developmental timing of expression of this allele would impact tumor formation we expressed the same erbB2 allele under the endogenous promoter in the germline of mice. Our recent report on these mice has revealed that mice expressing the activated erbB2 allele in the germline did not develop tumors although mice expressing an identical allele specifically in the mammary gland at equal levels developed tumors with a high penetrance. These recent reports are reviewed herein and taken together suggest that the developmental window of expression of a potent oncogene may impact tumorigenesis.
Andrechek
Eran R
ER
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
Muller
William J
WJ
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D008321:Mammary Glands, Animal / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D009857:Oncogenes / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases