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Publication : Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer.

First Author  Rottenberg S Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  29 Pages  12117-22
PubMed ID  17626183 Mgi Jnum  J:126564
Mgi Id  MGI:3761580 Doi  10.1073/pnas.0702955104
Citation  Rottenberg S, et al. (2007) Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer. Proc Natl Acad Sci U S A 104(29):12117-22
abstractText  We have studied in vivo responses of 'spontaneous' Brca1- and p53-deficient mammary tumors arising in conditional mouse mutants to treatment with doxorubicin, docetaxel, or cisplatin. Like human tumors, the response of individual mouse tumors varies, but eventually they all become resistant to the maximum tolerable dose of doxorubicin or docetaxel. The tumors also respond well to cisplatin but do not become resistant, even after multiple treatments in which tumors appear to regrow from a small fraction of surviving cells. Classical biochemical resistance mechanisms, such as up-regulated drug transporters, appear to be responsible for doxorubicin resistance, rather than alterations in drug-damage effector pathways. Our results underline the promise of these mouse tumors for the study of tumor-initiating cells and of drug therapy of human cancer.
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