Wood L J, Maher J F, Bunton T E, Resar L M
Hematology Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 2000 Aug 1;60(15):4256-61.
The HMG-I gene family encodes high mobility group proteins originally identified as nonhistone chromosomal binding proteins. HMG-I and -Y proteins are alternatively spliced products of the same mRNA; HMG-C is encoded by a separate gene. The HMG-I proteins function as architectural chromatin-binding proteins that bind to the narrow groove of AT-rich regions in double-stranded DNA. Recent studies indicate an important role for HMG-I proteins in regulating gene expression. Moreover, increased expression of the HMG-I, -Y, and -C proteins correlates with cellular proliferation and neoplastic transformation in several cell types and human cancers. Previous work from our laboratory has shown that HMG-I is a direct c-Myc target gene that is involved in Myc-mediated neoplastic transformation. In this report, we show that increased expression of HMG-Y or -C leads to transformation with anchorage-independent cell growth in two experimental cell lines in a manner similar to that of HMG-I or c-Myc. Moreover, Rat la cells overexpressing HMG-Y or -C form tumors in nude mice analogous to Rat 1a cells overexpressing HMG-I or c-Myc. Distant metastases developed in animals injected with cells overexpressing HMG-I or -C. Our findings suggest that the HMG-I gene family is involved in neoplastic transformation and may represent a new family of oncogenes important in the pathogenesis of several human cancers.
HMG-I基因家族编码高迁移率族蛋白，最初被鉴定为非组蛋白染色体结合蛋白。HMG-I和-Y蛋白是同一mRNA的可变剪接产物；HMG-C由一个单独的基因编码。HMG-I蛋白作为结构染色质结合蛋白，与双链DNA中富含AT的区域的窄沟结合。最近的研究表明HMG-I蛋白在调节基因表达中起重要作用。此外，HMG-I、-Y和-C蛋白的表达增加与几种细胞类型和人类癌症中的细胞增殖和肿瘤转化相关。我们实验室以前的工作表明，HMG-I是一个直接的c-Myc靶基因，参与Myc介导的肿瘤转化。在本报告中，我们表明HMG-Y或-C的表达增加会导致两种实验细胞系中出现不依赖贴壁的细胞生长转化，其方式与HMG-I或c-Myc相似。此外，过表达HMG-Y或-C的大鼠1a细胞在裸鼠中形成肿瘤，类似于过表达HMG-I或c-Myc的大鼠1a细胞。在注射过表达HMG-I或-C细胞的动物中出现了远处转移。我们的研究结果表明，HMG-I基因家族参与肿瘤转化，可能代表一个在几种人类癌症发病机制中起重要作用的新癌基因家族。
