Abstract

The data presented in this article are related to the research paper entitled “The biological age linked to oxidative stress modifies breast cancer aggressiveness” (M.M. Sáez-Freire, A. Blanco-Gómez, S. Castillo-Lluva, A. Gómez-Vecino, J.M. Galvis-Jiménez, C. Martín-Seisdedos, M. Isidoro-García, L. Hontecillas-Prieto, M.B. García-Cenador, F.J. García-Criado, M.C. Patino-Alonso, P. Galindo-Villardón, J.H. Mao, C. Prieto, A. Castellanos-Martín, L. Kaderali, J. Pérez-Losada). The data shown were obtained from a population of transgenic mice, MMTV-Erbb2/Neu, with different susceptibility to breast cancer and a mixed genetic background generated by backcrossing. It was observed that the aggressiveness of breast cancer negatively correlates with age, being lower in chronologically old mice, similar to what occurs in humans. Given that oxidative stress is associated with tumour susceptibility and the degree of aging, the association between the aggressiveness of breast cancer and multiple intermediate phenotypes directly or indirectly related to oxidative stress was studied. Using a mathematical model, we defined biological age and the degree of aging as the difference between biological and chronological ages. As a result, we observed that biologically old mice predominated among those that developed the disease early on, that is, those that were chronologically young. We then identified the specific and common genetic components of Quantitative Trait loci or QTL associated with different evolution of breast cancer, the intermediate phenotypes related to oxidative stress studied, the biological age and the degree of aging. Lastly, we showed that the expression pattern in the livers of biologically old mice were enriched in signalling pathways related to inflammation and response to infections; whereas the biologically young mice exhibited enriched pathways related to mitochondrial activity. For the explanation and discussion of these data refer to the research article cited above.

Highlights

  • María del Mar Sáez-Freire a,b,c,1, Adrián Blanco-Gómez a,b,1, Sonia Castillo-Lluva a,b,d, Aurora Gómez-Vecino a,b, Julie Milena Galvis-Jiménez a,b,e, Carmen Martín-Seisdedos b,f, María Isidoro-García b,f, Lourdes Hontecillas-Prieto a,b, María Begoña García-Cenador b,g, Francisco Javier García-Criado b,g, María Carmen Patino-Alonso b,h, Purificación Galindo-Villardón b,i,h, Jian-Hua Mao i, Carlos Prieto j, Andrés Castellanos-Martín a,b,n,2, Lars Kaderali k,nn,2, Jesús Pérez-Losada a,b,n,2 a Instituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC)

  • We identified the specific and common genetic components of Quantitative Trait loci or QTL associated with different evolution of breast cancer, the intermediate phenotypes related to oxidative stress studied, the biological age and the degree of aging

  • We identified the quantitative genetic component associated with the aggressiveness of breast cancer, aging and different intermediate phenotypes of oxidative stress

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Summary

Tumour pathophenotypes

Female transgene-positive mice were monitored and palpated once a week for the manifestation of primary mammary tumours. The following local tumour progression traits were considered: number of tumours - all visible tumours at necropsy; and local tumour progression parameters. These parameters included: (i) tumour volume, estimated every week using the formula [11]: Tumour volume 1⁄4 length  width . Levels of phosphorylated and total AKT2, AKT3, mTOR and total ERK were measured using the Sandwich ELISA Kit (Pathscan Cell Signaling Technology, Danvers, MA, USA) and phospho-AKT2 (Ser474) (catalogue number 7932), total AKT2 (catalogue number 7930, phospho-AKT3 (Ser472) (catalogue number 7942), total AKT3 (catalogue number 7934), phospho-mTOR (Ser2481) (catalogue number 7978), phospho-mTOR (Ser2448) (catalogue number 7976, total mTOR (catalogue number 7974) and total p44/42 MAPK (ERK1/2) (catalogue number 7050). Phospho-Akt (Thr308) (catalogue number 7144), phospho-AKT1 (Ser473) (catalogue number 7143), total AKT1 (catalogue number 7142) and phospho-P44/42 MAPK (Thr202/ Tyr204) (catalogue number 7246) were quantified

Quantification of telomere length
Statistical analysis
SNP genotyping
Linkage analysis
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