Ectopic vasopressin expression in MMTV-Wnt-1 transgenic mice modifies mammary tumor differentiation and pathology.
A transgenic mouse model has been developed to test the involvement of ectopic neuropeptide production as a secondary factor in cancer. Mice bearing a mouse mammary tumor virus-vasopressin (MMTV-VP) fusion transgene synthesized authentic vasopressin in mammary ducts and alveoli, but this had no effect on mammary gland development and growth. Mice bearing the MMTV-VP transgene were then mated with mice bearing the MMTV-Wnt-1 transgene to produce bitransgenic animals. Two types of mammary tumor develop in MMTV-Wnt-1 mice; type A mammary adenocarcinomas are uniform with fine acinar structure composed of small epithelial cells arranged to form round cavities and elongated tubules, while adenocarcinoma type B tumors have acinar areas, cystic spaces filled with blood or fluid, intracystic papillary projections, and cords as well as sheets of cells. Compared to the MMTV-Wnt-1 mice, the bitransgenic animals developed proportionally less type B tumors. Further, type B mammary adenocarcinomas from bitransgenic mice exhibited increased proliferation and growth, as judged by mitotic index and argyrophilic nucleolar organizer region counts, compared to type B tumors from MMTV-Wnt-1 mice. These data provide evidence that ectopic neuropeptide production can modulate the development of tumors in vivo.
Chooi
K F
KF
Neuropeptide Laboratory, Institute of Molecular and Cell Biology, Republic of Singapore.
Carter
D A
DA
Biswas
S
S
Lightman
S L
SL
Ho
M Y
MY
Murphy
D
D
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017668:Age of Onset; D000818:Animals; D003001:Cloning, Molecular; D005260:Female; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009697:Nucleolus Organizer Region; D010306:Parotid Gland / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D014667:Vasopressins / Q000096:biosynthesis*
D014667:Vasopressins