Down-regulation of β-F1-ATPase (the catalytic subunit of the mitochondrial H+-ATP synthase) is a hallmark of many human tumours. The expression level of β-F1-ATPase provides a marker of the prognosis of cancer patients, as well as of the tumour response to chemotherapy. However, the mechanisms that participate in down-regulating its expression in human tumours remain unknown. In the present study, we have investigated the expression of β-F1-ATPase mRNA (termed β-mRNA) in breast, colon and lung adenocarcinomas and squamous carcinomas of the lung. Despite the down-regulation of the protein, tumour β-mRNA levels remained either unchanged (breast and lung adenocarcinomas) or significantly increased (colon and squamous lung carcinomas) when compared with paired normal tissues, suggesting a specific translation-masking event for β-mRNA in human cancer. Consistently, we show using cell-free translation assays that a large fraction (~70%) of protein extracts derived from breast and lung adenocarcinomas specifically repress the translation of β-mRNA. We show that the 3′UTR (3′ untranslated region) of human β-mRNA is a relevant cis-acting element required for efficient translation of the transcript. However, an RNA chimaera bearing the 3′UTR of human β-mRNA does not recapitulate the inhibitory effect of tumour extracts on β-mRNA translation. Overall, the findings of the present study support the hypothesis that down-regulation of the bioenergetic activity of mitochondria in human tumours is exerted by translation silencing of β-mRNA.
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Research Article|
February 24 2010
Selective inhibition of β-F1-ATPase mRNA translation in human tumours
Imke M. Willers;
Imke M. Willers
1
*Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Universidad Autónoma de Madrid, 28049 Madrid, Spain
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Antonio Isidoro;
Antonio Isidoro
1
*Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Universidad Autónoma de Madrid, 28049 Madrid, Spain
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Álvaro D. Ortega;
Álvaro D. Ortega
*Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Universidad Autónoma de Madrid, 28049 Madrid, Spain
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Pedro L. Fernández;
Pedro L. Fernández
†Departamento de Anatomía Patológica, IDIBAPS, Hospital Clínico y Universidad de Barcelona, 08036 Barcelona, Spain
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José M. Cuezva
José M. Cuezva
2
*Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Universidad Autónoma de Madrid, 28049 Madrid, Spain
2To whom correspondence should be addressed (email jmcuezva@cbm.uam.es).
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Publisher: Portland Press Ltd
Received:
October 09 2009
Revision Received:
December 18 2009
Accepted:
December 23 2009
Accepted Manuscript online:
December 23 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 426 (3): 319–326.
Article history
Received:
October 09 2009
Revision Received:
December 18 2009
Accepted:
December 23 2009
Accepted Manuscript online:
December 23 2009
Citation
Imke M. Willers, Antonio Isidoro, Álvaro D. Ortega, Pedro L. Fernández, José M. Cuezva; Selective inhibition of β-F1-ATPase mRNA translation in human tumours. Biochem J 15 March 2010; 426 (3): 319–326. doi: https://doi.org/10.1042/BJ20091570
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