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040			_cH12O
041			_aeng
100			_92401 _aCruz Bermúdez, Alberto _eInstituto de Investigación i+12
100			_92795 _aGallardo, María Esther _eInstituto de Investigación i+12
100			_9860 _aFernández Moreno, Miguel Ángel _eInstituto de Investigación i+12
100			_9862 _aGaresse, Rafael _eInstituto de Investigación i+12
245	0	0	_aEnhanced tumorigenicity by mitochondrial DNA mild mutations. _h[artículo]
260			_bOncotarget, _c2015
300			_a6(15):13628-43.
500			_aFormato Vancouver: Cruz Bermúdez A, Vallejo CG, Vicente Blanco RJ, Gallardo ME, Fernández Moreno MÁ, Quintanilla M et al. Enhanced tumorigenicity by mitochondrial DNA mild mutations. Oncotarget. 2015 May 30;6(15):13628-43.
501			_aPMID: 25909222 PMC4537038
504			_aContiene 64 referencias
505			_aErratum in: Oncotarget. 2020 Mar 17;11(11):1006. .
520			_aTo understand how mitochondria are involved in malignant transformation we have generated a collection of transmitochondrial cybrid cell lines on the same nuclear background (143B) but with mutant mitochondrial DNA (mtDNA) variants with different degrees of pathogenicity. These include the severe mutation in the tRNALys gene, m.8363G>A, and the three milder yet prevalent Leber's hereditary optic neuropathy (LHON) mutations in the MT-ND1 (m.3460G>A), MT-ND4 (m.11778G>A) and MT-ND6 (m.14484T>C) mitochondrial genes. We found that 143B ρ0 cells devoid of mtDNA and cybrids harboring wild type mtDNA or that causing severe mitochondrial dysfunction do not produce tumors when injected in nude mice. By contrast cybrids containing mild mutant mtDNAs exhibit different tumorigenic capacities, depending on OXPHOS dysfunction.The differences in tumorigenicity correlate with an enhanced resistance to apoptosis and high levels of NOX expression. However, the final capacity of the different cybrid cell lines to generate tumors is most likely a consequence of a complex array of pro-oncogenic and anti-oncogenic factors associated with mitochondrial dysfunction.Our results demonstrate the essential role of mtDNA in tumorigenesis and explain the numerous and varied mtDNA mutations found in human tumors, most of which give rise to mild mitochondrial dysfunction.
710			_9625 _aInstituto de Investigación imas12
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537038/ _yAcceso libre
942			_2ddc _cART _n0