Risinger John I, Custer Mary, Feigenbaum Lionel, Simpson R Mark, Hoover Shelley B, Webster Joshua D, Chandramouli Gadisetti V R, Tessarollo Lino, Barrett J Carl
Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, Michigan; Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Mol Carcinog. 2014 Aug;53(8):610-24. doi: 10.1002/mc.22009. Epub 2013 Feb 8.
The KAI1/CD82 tetraspanin is a widely expressed cell surface molecule thought to organize diverse cellular signaling processes. KAI1/CD82 suppresses metastasis but not tumorigenicity, establishing it as one of a class of metastasis suppressor genes. In order to further assess its functions, we have characterized the phenotypic properties of Kai1/Cd82 deleted mice, including viability, fertility, lymphocyte composition, blood chemistry and tissue histopathology, and of their wild-type and heterozygote littermates. Interestingly, Kai1/Cd82(-/-) showed no obvious genotype associated defects in any of these processes and displayed no genotype associated histopathologic abnormalities after 12 or 18 months of life. Expression profiles of non-immortal, wild-type and Kai1/Cd82(-/-) mouse embryo fibroblast (MEFs) indicated distinct sex-specific and genotype-specific profiles. These data identify 191 and 1,271 differentially expressed transcripts (by twofold at P < 0.01) based on Kai1/CD82 genotype status in female and male MEFs, respectively. Differentially expressed genes in male MEFs were surprisingly enriched for cell division related processes, suggesting that Kai1/Cd82 may functionally affect these processes. This suggests that Kai/Cd82 has an unappreciated role in the early establishment of proliferation and division when challenged with a new environment that might play a role in adaptability to new metastatic sites.
KAI1/CD82四跨膜蛋白是一种广泛表达的细胞表面分子,被认为可组织多种细胞信号传导过程。KAI1/CD82抑制转移但不抑制肿瘤发生,使其成为一类转移抑制基因之一。为了进一步评估其功能,我们对Kai1/Cd82基因敲除小鼠及其野生型和杂合子同窝小鼠的表型特性进行了表征,包括活力、生育力、淋巴细胞组成、血液化学和组织组织病理学。有趣的是,Kai1/Cd82(-/-)在这些过程中均未表现出明显的与基因型相关的缺陷,并且在12或18个月龄后未显示出与基因型相关的组织病理学异常。非永生化的野生型和Kai1/Cd82(-/-)小鼠胚胎成纤维细胞(MEF)的表达谱表明存在明显的性别特异性和基因型特异性谱。这些数据分别基于雌性和雄性MEF中的Kai1/CD82基因型状态,鉴定出191个和1271个差异表达的转录本(P<0.01时为两倍)。雄性MEF中差异表达的基因令人惊讶地富集于细胞分裂相关过程,这表明Kai1/Cd82可能在功能上影响这些过程。这表明,当面对可能在适应新转移部位中起作用的新环境时,Kai/Cd82在增殖和分裂的早期建立中具有未被认识的作用。