2026-04-14T02:31:35Zhttps://recercat.cat/oai/request
oai:recercat.cat:10230/163982025-12-26T11:27:47Zcom_2072_6col_2072_452952
RECERCAT author Solé, Xavier author Hernández, Pilar author López de Heredia, Miguel de author Armengol i Dulcet, Lluís author Rodríguez Santiago, Benjamín author Gómez, Laia author Maxwell, Christopher A. author Aguilo, Fernando author Condom, Enric author Abril, Jesús author Pérez Jurado, Luis Alberto author Estivill, Xavier, 1955- author Nunes, Virginia author Capellá, Gabriel author Gruber, Stephen B. author Moreno, Víctor author Pujana Genestar, M. Ángel 2012-05-03T08:26:20Z2012-05-03T08:26:20Z2008 Background: Germline genetic variation is associated with the differential expression of many human genes. The phenotypic effects of this type of variation may be important when considering susceptibility to common genetic diseases. Three regions at 8q24 have recently been identified to independently confer risk of prostate cancer. Variation at 8q24 has also recently been associated with risk of breast and colorectal cancer. However, none of the risk variants map at or relatively close to known genes, with c-MYC mapping a few hundred kilobases distally. Results: This study identifies cis-regulators of germline c-MYC expression in immortalized lymphocytes of HapMap individuals. Quantitative analysis of c-MYC expression in normal prostate tissues suggests an association between overexpression and variants in Region 1 of prostate cancer risk. Somatic c-MYC overexpression correlates with prostate cancer progression and more aggressive tumor forms, which was also a pathological variable associated with Region 1. Expression profiling analysis and modeling of transcriptional regulatory networks predicts a functional association between MYC and the prostate tumor suppressor KLF6. Analysis of MYC/Myc-driven cell transformation and tumorigenesis substantiates a model in which MYC overexpression promotes transformation by down-regulating KLF6. In this model, a feedback loop through E-cadherin down-regulation causes further transactivation of c-MYC./nConclusion: This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene. © 2008 Solé et al. Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0/ info:eu-repo/semantics/openAccess Genètica humana -- Variació Genètica molecular Càncer -- Aspectes genètics Genetic and genomic analysis modeling of germline c-MYC overexpression and cancer susceptibility info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion