美国哥伦比亚大学放射学研究所，Herbert Irving综合癌症研究中心，临床肿瘤系，洛克菲勒大学分子生物学实验室，中国医学科学院基础医学研究所生物化学与分子生物学系等处的研究人员在最新一期的《癌症研究》（Cancer Research）上发表关于TGFBI与癌症发生的相关文章。
TGFBI基因表达的TGFBI蛋白是一种由转化生长因子β诱导的分泌蛋白，在早期的报道中发现该蛋白与癌症有关联，很可能成为癌症的一种生物学标记物。
体外实验研究发现如果细胞缺失TGFBI会导致细胞过度增殖，促进肿瘤血管生成，促成癌症发生。因此说，TGFBI蛋白具有抗肿瘤的功能，但是，TGFBI蛋白如何在活体内发挥作用，其作用的分子机制如何一直鲜为人知。为了深入了解TGFBI蛋白的作用机制，研究小组开展了下面的研究工作。
以小鼠为模型，将小鼠的TGFBI基因剔除掉，小鼠成为不表达TGFBI的缺陷型小鼠，结果表明，缺陷型小鼠更易罹患癌症，在7，12-二甲苯恩的作用下更易自发形成皮肤癌。研究者还发现，缺陷型的小鼠胚胎成纤维细胞更易发生染色体畸变，细胞增殖活性增强，细胞复制过程中过早进入S期（这些都有可能增强癌变的几率）。缺失TGFBI可能导致转录因子CREB激活，上调cyclin D1蛋白的表达。研究者发现，如果用遗传技术在小鼠的胚胎成纤维细胞中再导入TGFBI，可有效地逆转癌变的过程。
研究小组的实验结果首次证实TGFBI在活体内具有肿瘤抑制子的活性。该研究成果提示TGFBI可能成为诊断和治疗的靶位。（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Research，doi: 10.1158/0008-5472.CAN-08-1648，Tom K. Hei，Yongliang Zhao
TGFBI Deficiency Predisposes Mice to Spontaneous Tumor Development
Ye Zhang1,5, Gengyun Wen1, Genze Shao1,6, Cuidong Wang4, Chyuansheng Lin2, Hongbo Fang5, Adayabalam S. Balajee1, Govind Bhagat3, Tom K. Hei1 and Yongliang Zhao1
1 Center for Radiological Research, 2 Herbert Irving Comprehensive Cancer Center, and 3 Department of Clinical Pathology, Columbia University; 4 Laboratory of Molecular Biology, The Rockefeller University, New York, New York; 5 Department of Biochemistry and Molecular Biology, Chinese Academy of Medical Sciences and Peking union Medical College, Beijing, China; and 6 Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania
Loss of TGFBI, a secreted protein induced by transforming growth factor-β, has been implicated in cell proliferation, tumor progression, and angiogenesis by in vitro studies. However, in vivo antitumor functions of TGFBI as well as the underlying molecular mechanism are not well understood. To these aims, we have generated a mouse model with disruption of TGFBI genomic locus. Mice lacking TGFBI show a retarded growth and are prone to spontaneous tumors and 7,12-dimethylbenz(a)anthracene–induced skin tumors. In relation to wild-type (WT) mouse embryonic fibroblasts (MEF), TGFBI–/– MEFs display increased frequencies of chromosomal aberration and micronuclei formation and exhibit an enhanced proliferation and early S-phase entry. Cyclin D1 is up-regulated in TGFBI–/– MEFs, which correlates with aberrant activation of transcription factor cyclic AMP–responsive element binding protein (CREB) identified by chromatin immunoprecipitation and luciferase reporter assays. TGFBI reconstitution in TGFBI–/– cells by either retroviral infection with WT TGFBI gene or supplement with recombinant mouse TGFBI protein in the culture medium leads to the suppression of CREB activation and cyclin D1 expression, and further inhibition of cell proliferation. Cyclin D1 up-regulation was also identified in most of the tumors arising from TGFBI–/– mice. Our studies provide the first evidence that TGFBI functions as a tumor suppressor in vivo.
