PM-10CDCA7L FUNCTIONS AS A MALE-SPECIFIC ONCOGENE IN ASTROCYTOMA.

摘要: The most common types of primary brain tumors, astrocytoma and glioblastoma multiforme (GBM), are currently incurable. Both GBM show male predominance, with a to female ratio 1.42:1 1.58:1, respectively. We performed linkage analysis in the Nf1-/ + ;Trp53-/ cis (NPcis) mouse model astrocytoma/GBM identify male-specific gliomagenesis modifier further used combinatorial bioinformatics approaches as well cross-species comparisons prioritize candidate gene(s). Here, we showed that Cell division cycle-associated 7-like (CDCA7L), myc cotranscription factor, is oncogene astrocytoma/GBM. CDCA7L expression up-regulated cells compared normal brain, males showing higher levels than females both human mouse. shRNA-mediated knockdown led decreased cell growth viability male-derived cells, but not tumor Further mechanistic studies depletion induction cleaved Caspase-3 p27 reduction Cyclin D1 expression. Furthermore, Cdca7l overexpression promotes WT astrocytes only by inducing expression, astrocytes, suggesting oncogenic role for Strikingly, U87MG caused increase opposite what seen cells. Because male-female differences action hormone-independent, examined whether histone demethylase KDM5D regulates effects CDCA7L. found inhibits on Our data highlight sex-specificity tumorigenesis signaling pathways can be males, while being neutral or suppressive females. This has important implications application therapies patients.