Accession Number ADA575227
Title Myeloperoxidase in the Progression of Breast Cancer.
Publication Date Sep 2012
Media Count 17p
Personal Author B. M. Mueller
Abstract A high myeloperoxidase (MPO) expression genotype is strongly associated with better survival among women with breast cancer that undergo chemotherapy. The objective of this project is to find a mechanistic basis for this clinical observation. We examined the effect of human-type MPO expression in a mouse model for human breast cancer. We have crossed mice that carry the polyoma virus middle T oncogene (PyMT) and develop mammary tumors with mice that carry a human MPO (huMPO) transgene. We observed no difference in time of tumor onset or multifocal disease between PyMT/wt and PyMT/huMPO mice. However, huMPO results in reduced tumor growth. Most but not all mice of either genotype developed macroscopic lung metastasis. PyMT/huMPO mice have fewer metastatic foci than PyMT/wt mice and the difference is consistent with their smaller tumor burden. We found huMPO expressed in tumor cells in mammary tumors and metastases in PyMT/huMPO mice. We have considered different mechanisms by which MPO may be protective in breast cancer. One hypothesis was that MPO expressed in tumor-associated macrophages contributes to macrophage-mediated tumor suppression and augments the effect of chemotherapy. We found no evidence for a role of cytotoxic macrophages in the tumor suppressive effect of MPO. In contrast our data show that cytotoxic drugs and possibly other pro-apoptotic factors induce MPO expression and that MPO expressed in tumor cells appears to contribute to cell death in the presence of cytotoxic drugs. These results can provide the rationale to search for non-toxic treatments that induce MPO and that could be used in synergy with low dose chemotherapy protocols.
Keywords Anatomical models
Breast cancer
Cells(Biology)
Chemotherapy
Clinical medicine
Cytotoxic drugs
Cytotoxins
Death
Diseases
Dosage
Growth(Physiology)
Macrophages
Mammary glands
Metastasis
Mpo(Myeloperoxidase)
Neoplasms
Observation
Oncogenic viruses
Polyoma virus
Suppression
Survival(Personnel)
Viruses


 
Source Agency Non Paid ADAS
NTIS Subject Category 57B - Biochemistry
57E - Clinical Medicine
Corporate Author Torrey Pines Inst. for Molecular Studies, San Diego, CA.
Document Type Technical report
Title Note Final rept. 28 Aug 2009-27 Aug 2012.
NTIS Issue Number 1319
Contract Number W81XWH-09-1-0633

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