Tong S, Liss A S, You M, Bose H R
Section of Molecular Genetics and Microbiology and the Institute of Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1095, USA.
Oncogene. 2007 Apr 5;26(16):2318-29. doi: 10.1038/sj.onc.1210023. Epub 2006 Oct 2.
v-Rel is the oncogenic member of the Rel/NF-kappaB family of transcription factors and transforms hematopoietic cells and fibroblasts. Differential display was employed to identify target genes that exhibit altered expression in v-Rel transformed cells. One of the cDNAs identified encodes the chicken ortholog of TC10, a member of the Rho small GTPase family. The expression of TC10 was increased in v-Rel-transformed chicken embryonic fibroblasts (CEFs) 3 to 6-fold relative to control cells at both the RNA and protein levels. An elevated level of active, GTP-bound TC10 was also detected in v-Rel-transformed cells relative to control cells. Expression of a dominant-negative TC10 mutant (TC10T32N) decreased the colony formation potential of v-Rel-transformed cells. Furthermore, overexpression of wild-type TC10 or a gain-of-function mutant (TC10Q76L) greatly enhanced the ability of v-Rel transformed CEFs to form colonies in soft agar. In addition to enhance the transformation potential of v-Rel, the overexpression of wild-type TC10 or the gain-of-function mutant alone enhanced the saturation density of CEFs and was sufficient for their anchorage-independent growth in vitro. These results indicate that elevated TC10 activity contributes to v-Rel-mediated transformation of CEFs and demonstrate for the first time that a Rho factor alone is capable of inducing the in vitro transformation of primary cells.
v-Rel是转录因子Rel/NF-κB家族的致癌成员，可转化造血细胞和成纤维细胞。采用差异显示技术来鉴定在v-Rel转化细胞中表达发生改变的靶基因。鉴定出的一个cDNA编码Rho小GTP酶家族成员TC10的鸡直系同源物。在v-Rel转化的鸡胚成纤维细胞（CEF）中，TC10在RNA和蛋白质水平上相对于对照细胞的表达增加了3至6倍。相对于对照细胞，在v-Rel转化的细胞中也检测到活性GTP结合的TC10水平升高。显性负性TC10突变体（TC10T32N）的表达降低了v-Rel转化细胞的集落形成潜力。此外，野生型TC10或功能获得性突变体（TC10Q76L）的过表达大大增强了v-Rel转化的CEF在软琼脂中形成集落的能力。除了增强v-Rel的转化潜力外，野生型TC10或功能获得性突变体单独过表达还增强了CEF的饱和密度，并且足以使其在体外进行不依赖贴壁的生长。这些结果表明，升高的TC10活性有助于v-Rel介导的CEF转化，并首次证明单独的Rho因子能够诱导原代细胞的体外转化。
