Three loci modify growth of a transgene-induced mammary tumor: suppression of proliferation associated with decreased microvessel density.
In earlier studies it was observed that the genetic background significantly affected the phenotype of a transgene-induced mammary tumor. Tumors arising in an (I/LnJ x PyMT) F1 hybrid background appeared earlier than in the FVB/N-TgN(MMTV-PyVT)(634Mul) parent, but accumulated less tumor mass, indicating a net decrease in tumor growth. Quantitative genetic mapping in a backcross identified three loci that were associated with the decreased proliferative capacity of the I/LnJ F1 tumors. Molecular analysis of the tumors suggests that these loci may act by restricting the tumor's ability to recruit microvessels. The three loci, designated Mmtg1-3, are unlinked to the angiogenic genes Fgf2, Flt1, Flk4, Flk1, Vegf, and Vegfc, as well as the precursors of the endogenous antiangiogenic molecules angiostatin and endostatin. The Mmtg loci may therefore provide novel targets for antiangiogenic therapeutic strategies.
Le Voyer
T
T
Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA.
Rouse
J
J
Lu
Z
Z
Lifsted
T
T
Williams
M
M
Hunter
K W
KW
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001808:Blood Vessels / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019655:Quantitative Trait, Heritable
D019394:Ki-67 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1