Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice.
Using a Cre-lox-based genetic labeling technique, we have recently discovered a parity-induced mammary epithelial subtype that is abundant in nonlactating and nonpregnant, parous females. These mammary epithelial cells serve as alveolar progenitors in subsequent pregnancies, and transplantation studies revealed that they possess features of multipotent progenitors such as self-renewal and the capability to contribute to ductal and alveolar morphogenesis. Here, we report that these cells are the cellular targets for transformation in MMTV-neu transgenic mice that exhibit accelerated mammary tumorigenesis in multiparous animals. The selective ablation of this epithelial subtype reduces the onset of tumorigenesis in multiparous MMTV-neu transgenics. There is, however, experimental evidence to suggest that parity-induced mammary epithelial cells may not be the only cellular targets in other MMTV-promoter-based transgenic strains. In particular, the heterogeneous MMTV-wnt1 lesions predominantly express the ductal differentiation marker Nkcc1 that is absent in MMTV-neu-derived tumors. Our observations support the idea that tumors originate from distinctly different epithelial subtypes in selected MMTV-promoter-driven cancer models and that diverse oncogenes might exert discrete effects on particular mammary epithelial subtypes.
Henry
MaLinda D
MD
Eppley Institute for Research in Cancer and Allied Diseases and the Department of Pathology and Microbiology, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Triplett
Aleata A
AA
Oh
Keon Bong
KB
Smith
Gilbert H
GH
Wagner
Kay-Uwe
KU
D000818:Animals; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D018734:Genes, erbB-2; D019426:Integrases / Q000502:physiology; D008321:Mammary Glands, Animal / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000209:etiology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010298:Parity; D011401:Promoter Regions, Genetic
C045073:Cre recombinase; D019426:Integrases