Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2407-11-191
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dc.titleMitochondrial targeted catalase suppresses invasive breast cancer in mice
dc.contributor.authorGoh, Jorming
dc.contributor.authorEnns, Linda
dc.contributor.authorFatemie, Soroosh
dc.contributor.authorHopkins, Heather
dc.contributor.authorMorton, John
dc.contributor.authorPettan-Brewer, Christina
dc.contributor.authorLadiges, Warren
dc.date.accessioned2022-04-21T09:25:58Z
dc.date.available2022-04-21T09:25:58Z
dc.date.issued2011-05-23
dc.identifier.citationGoh, Jorming, Enns, Linda, Fatemie, Soroosh, Hopkins, Heather, Morton, John, Pettan-Brewer, Christina, Ladiges, Warren (2011-05-23). Mitochondrial targeted catalase suppresses invasive breast cancer in mice. BMC CANCER 11 (1). ScholarBank@NUS Repository. https://doi.org/10.1186/1471-2407-11-191
dc.identifier.issn1471-2407
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/219461
dc.description.abstractBackground: Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential.Methods: Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined.Results: PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects.Conclusion: Targeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer.Please see related commentary article: http://www.biomedcentral.com/1741-7015/9/62. © 2011 Goh et al; licensee BioMed Central Ltd.
dc.language.isoen
dc.publisherBIOMED CENTRAL LTD
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectTUMOR PROGRESSION
dc.subjectOXIDATIVE STRESS
dc.subjectDNA-DAMAGE
dc.subjectCELLS
dc.subjectMETASTASIS
dc.subjectMECHANISM
dc.subjectHYPOXIA
dc.subjectOVEREXPRESSION
dc.subjectMACROPHAGES
dc.subjectINSTABILITY
dc.typeArticle
dc.date.updated2022-04-21T02:13:33Z
dc.contributor.departmentPHYSIOLOGY
dc.description.doi10.1186/1471-2407-11-191
dc.description.sourcetitleBMC CANCER
dc.description.volume11
dc.description.issue1
dc.published.statePublished
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