Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis.
To determine the impact of tumor progression on the reversibility of Neu-induced tumorigenesis, we have used the tetracycline regulatory system to conditionally express activated Neu in the mammary epithelium of transgenic mice. When induced with doxycycline, bitransgenic MMTV-rtTA/TetO-NeuNT mice develop multiple invasive mammary carcinomas, essentially all of which regress to a clinically undetectable state following transgene deinduction. This demonstrates that Neu-initiated tumorigenesis is reversible. Strikingly, extensive lung metastases arising from Neu-induced mammary tumors also rapidly and fully regress following the abrogation of Neu expression. However, despite the near universal dependence of both primary tumors and metastases on Neu transgene expression, most animals bearing fully regressed Neu-induced tumors ultimately develop recurrent tumors that have progressed to a Neu-independent state.
Moody
Susan E
SE
Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Sarkisian
Christopher J
CJ
Hahn
Kristina T
KT
Gunther
Edward J
EJ
Pickup
Steven
S
Dugan
Katherine D
KD
Innocent
Nathalie
N
Cardiff
Robert D
RD
Schnall
Mitchell D
MD
Chodosh
Lewis A
LA
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation; D004318:Doxycycline; D004848:Epithelium / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D018734:Genes, erbB-2 / Q000235:genetics*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008279:Magnetic Resonance Imaging; D008321:Mammary Glands, Animal / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009368:Neoplasm Transplantation; D012074:Remission Induction / Q000379:methods*; D019076:Transgenes
D004318:Doxycycline