3 years ago

Mitochondrial haplotype alters mammary cancer tumorigenicity and metastasis in an oncogenic driver- dependent manner.

Amanda E Brinker, Trevor T Tsue, Danny R Welch, Roy A Jensen, Devin C Koestler, Carolyn J Vivian
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 and 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 v 293 v 225 days), fewer pulmonary metastases (5 v 7 v 15) and differences in size of lung metastases (1.2 v 1.4 v 1.0 mm diameter) compared to FVB/NJ mtDNA. Although PyMT-driven tumors showed altered primary and metastatic profiles in previous studies, depending upon nuclear and mtDNA haplotype, the magnitude 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.

Publisher URL: http://doi.org/10.1158/0008-5472.CAN-17-2194

DOI: 10.1158/0008-5472.CAN-17-2194

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.