Hormonal modulation of neu-induced mammary carcinogenesis: evidence against a single-step induction of mammary cancer by neu.
When activated by a point mutation in its transmembrane domain neu is an extremely potent transforming oncogene when expressed in rodent mammary parenchyma. This extreme potency led Muller et al. (13) to suggest the possibility that neu might transform mammary cells by a single step. A corollary to a single-step transformation hypothesis is that transformation efficiency cannot be modulated. Here we test this corollary by introducing mutated neu into in situ rat mammary cells using retroviral vectors and following infection by hormonally modulating recipient rats. Hormonal modulation included raising prolactin levels and lowering glucocorticoid levels. This modulation promotes radiation, chemical and ras initiated mammary carcinogenesis. Here we report that this hormonal promotion protocol also increased the yield of mammary carcinomas following the introduction of the mutated neu gene. We conclude that mutated neu is not a single-step transformer but is a very potent event in the multistage process of mammary carcinogenesis.
Tai
Y T
YT
University of Wisconsin-Madison, Department of Human Oncology 53792, USA.
Gould
M N
MN
D016475:3T3 Cells / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003043:Cocarcinogenesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D005938:Glucocorticoids / Q000172:deficiency*; D006966:Hyperprolactinemia / Q000503:physiopathology*; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D017354:Point Mutation; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D005938:Glucocorticoids; D011388:Prolactin; D018719:Erb-b2 Receptor Tyrosine Kinases