title: Development of mouse models of malignant phyllodes tumors by transplantation of syngeneic mammary gland cells expressing mutant H-Ras.
abstract: Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast with epithelial and stromal components, and surgical resection is the standard and only available treatment for malignant PTs. To provide a better understanding of these tumors, we developed mouse models that recapitulate the pathological and clinical properties of human malignant PTs. Mouse undifferentiated mammary gland cells were infected with a retrovirus encoding the human oncoprotein H-RasG12V, and the infected cells were transplanted orthotopically into the mammary fat pads of syngeneic mice. The transplanted cells showed a high tumorigenic activity, with the resulting tumors manifesting pathological characteristics including stromal overgrowth similar to those of human malignant PTs. The tumors also showed high rates of both local recurrence and lung metastasis. Our models may prove useful for studies of the pathophysiology of malignant PTs as well as facilitate the development of new treatments.
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Takamoto
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D017690:Cell Transplantation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D011905:Genes, ras; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D003557:Phyllodes Tumor / Q000235:genetics / Q000473:pathology; D012190:Retroviridae / Q000235:genetics