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Full-Text Articles in Medicine and Health Sciences
Radiation Acts On The Microenvironment To Affect Breast Carcinogenesis By Distinct Mechanisms That Decrease Cancer Latency And Affect Tumor Type, Karen Dunphy, D.H. Nguyen, H.A. Oketch-Rabah, I. Illa-Bochaca, F.C. Geyer, J.S. Reis-Filho, J.H. Mao, S.A. Ravani, J. Zavadil, A.D. Borowsky, J.D. Jeryy
Radiation Acts On The Microenvironment To Affect Breast Carcinogenesis By Distinct Mechanisms That Decrease Cancer Latency And Affect Tumor Type, Karen Dunphy, D.H. Nguyen, H.A. Oketch-Rabah, I. Illa-Bochaca, F.C. Geyer, J.S. Reis-Filho, J.H. Mao, S.A. Ravani, J. Zavadil, A.D. Borowsky, J.D. Jeryy
Karen Dunphy
Tissue microenvironment is an important determinant of carcinogenesis. We demonstrate that ionizing radiation, a known carcinogen, affects cancer frequency and characteristics by acting on the microenvironment. Using a mammary chimera model in which an irradiated host is transplanted with oncogenic Trp53 null epithelium, we show accelerated development of aggressive tumors whose molecular signatures were distinct from tumors arising in nonirradiated hosts. Molecular and genetic approaches show that TGFβ mediated tumor acceleration. Tumor molecular signatures implicated TGFβ, and genetically reducing TGFβ abrogated the effect on latency. Surprisingly, tumors from irradiated hosts were predominantly estrogen receptor negative. This effect was TGFβ independent …
Repression Of Mammary Stem/Progenitor Cells By P53 Is Mediated By Notch And Separable From Apoptotic Activity, Karen Dunphy, L. Tao, C. Bigelow, H. Yan, J.D. Jerry
Repression Of Mammary Stem/Progenitor Cells By P53 Is Mediated By Notch And Separable From Apoptotic Activity, Karen Dunphy, L. Tao, C. Bigelow, H. Yan, J.D. Jerry
Karen Dunphy
Breast cancer is the most common tumor among women with inherited mutations in the p53 gene (Li-Fraumeni syndrome). The tumors represent the basal-like subtype, which has been suggested to originate from mammary stem/progenitor cells. In mouse mammary epithelium, mammosphere-forming potential was increased with decreased dosage of the gene encoding the p53 tumor suppressor protein (Trp53). Limiting dilution transplantation also showed a 3.3-fold increase in the frequency of long-term regenerative mammary stem cells in Trp53−/− mice. The repression of mammospheres by p53 was apparent despite the absence of apoptotic responses to radiation indicating a dissociation of these two activities of p53. …