title: Rab3a promotes brain tumor initiation and progression.
abstract: The Rab protein family is composed of small GTP-binding proteins involved in intracellular vesicle trafficking. In particular, Rab3a which is one of four Rab3 proteins (a, b, c, and d isoforms) is associated with synaptic vesicle trafficking in normal brain. However, despite the elevated level of Rab3a in tumors, its role remains unclear. Here we report a tumorigenic role of Rab3a in brain tumors. Elevated level of Rab3a expression in human was confirmed in both glioma cell lines and glioblastoma multiforme patient specimens. Ectopic Rab3a expression in glioma cell lines and primary astrocytes promoted cell proliferation by increasing cyclin D1 expression, induced resistance to anti-cancer drug and irradiation, and accelerated foci formation in soft agar and tumor formation in nude mice. The overexpression of Rab3a augmented the tumorsphere-forming ability of glioma cells and p53(-/-) astrocytes and increased expression levels of various stem cell markers. Taken together, our results indicate that Rab3a is a novel oncogene involved in glioma initiation and progression.
authors: Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors: Jun-Kyum
authors: JK
authors: Kim
authors: Seung-Yup
authors: SY
authors: Lee
authors: Chang-Won
authors: CW
authors: Park
authors: Suk-Hwang
authors: SH
authors: Park
authors: Jinlong
authors: J
authors: Yin
authors: Jaebong
authors: J
authors: Kim
authors: Jae-Bong
authors: JB
authors: Park
authors: Jae-Yong
authors: JY
authors: Lee
authors: Hyunggee
authors: H
authors: Kim
authors: Sung-Chan
authors: SC
authors: Kim
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D019938:Cyclin D1; D020826:rab3A GTP-Binding Protein