期刊
CANCER RESEARCH
卷 77, 期 24, 页码 6941-6949出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-17-2194
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资金
- Susan G. Komen for the Cure [SAC11037]
- National Foundation for Cancer Research
- NIH [R01-CA134981, P30-CA168524]
- Biostatistics & Informatics Shared Resource (BISR) of the University of Kansas Cancer Center [P30 CA168524]
- Kansas Bioscience Authority
- Biomedical Research Training Program Fellowship
Using a novel mouse model, a mitochondrial-nuclear exchange model termed MNX, we tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu) 202Mul/J (Her2) transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA with either FVB/NJ, C57BL/6J, or BALB/cJ mtDNA. Pups receiving the C57BL/6J or BALB/cJ mitochondrial genome (i.e., females crossed with Her2 males) showed significantly (P < 0.001) longer tumor latency (262 vs. 293 vs. 225 days), fewer pulmonary metastases (5 vs. 7 vs. 15), and differences in size of lung metastases (1.2 vs. 1.4 vs. 1.0 mm diameter) compared with FVB/NJ mtDNA. Although polyoma virus middle T-driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear andmtDNA haplotype, th emagnitude and direction of changes were not the same in the HER2-driven mammary carcinomas. Collectively, these results establish mitochondrial polymorphisms as quantitative trait loci in mammary carcinogenesis, and they implicate distinct interactions between tumor drivers and mitochondria as critical modifiers of tumorigenicity and metastasis. (C) 2017 AACR.
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