The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers
作者： Kwai Wa Cheng , John P Lahad , Wen-lin Kuo , Anna Lapuk , Kyosuke Yamada
DOI: 10.1038/NM1125
关键词: Cancer cell 、 Bcl-2 Homologous Antagonist-Killer Protein 、 Cancer research 、 Apoptosis 、 Anoikis 、 PI3K/AKT/mTOR pathway 、 Kinase 、 Biology 、 Bcl-2-associated X protein 、 RNA interference
摘要: High-density array comparative genomic hybridization (CGH) showed amplification of chromosome 1q22 centered on the RAB25 small GTPase, which is implicated in apical vesicle trafficking, approximately half ovarian and breast cancers. mRNA levels were selectively increased stage III IV serous epithelial cancers compared to other genes within amplified region, implicating as a driving event development amplicon. Increased DNA copy number or RNA level was associated with markedly decreased disease-free survival overall cancers, respectively. Forced expression anchorage-dependent anchorage-independent cell proliferation, prevented apoptosis anoikis, including that induced by chemotherapy, aggressiveness cancer cells vivo. The inhibition decrease proapoptotic molecules, BAK BAX, activation antiapoptotic phosphatidylinositol 3 kinase (PI3K) AKT pathway, providing potential mechanisms for effects tumor aggressiveness. Overall, these studies implicate RAB25, thus RAB family G proteins,
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