The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression

BMC Cancer

Research Article

Gengyun Wen¹  Yongliang Zhao¹  Jian Tong²  Bingyan Li³  Tom K Hei⁴ 

[1] Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, NY, USA;School of Radiation Medicine and Public Health, Soochow University, Suzhou, China;School of Radiation Medicine and Public Health, Soochow University, Suzhou, China;Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, NY, USA;School of Radiation Medicine and Public Health, Soochow University, Suzhou, China;Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, NY, USA;Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA;Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th St, 10032, New York, NY, USA;

关键词: TGFBI;    Tumor suppressor;    Mesothelioma;    Breast tumor;    Proliferation;   

DOI  :  10.1186/1471-2407-12-239

 received in 2011-11-13, accepted in 2012-05-21,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTransforming growth factor β induced (TGFBI) product, an extracellular matrix (ECM) protein, has been implicated as a putative tumor suppressor in recent studies. Our previous findings revealed that expression of TGFBI gene is down-regulated in a variety of cancer cell lines and clinical tissue samples. In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer.MethodsCells were stably transfected with pRc/CMV2-TGFBI and pRc/CMV2-empty vector with Lipofectamine Plus. Ectopic expression of TGFBI was quantified by using quantitative PCR and Western-blotting. Characterization of cell viability was assessed using growth curve, clonogenic survival and soft agar growth. The potential of tumor formation was evaluated by an in vivo mouse model. Cell cycle was analyzed via flow cytometry. Expressions of p21, p53, p16 and p14 were examined using Western-blotting. Senescent cells were sorted by using a Senescence β-Galactosidase Staining Kit. Telomerase activity was measured using quantitative telomerase detection kit.ResultsIn this study, an ectopic expression of TGFBI in two types of cancer cell lines, a mesothelioma cell line NCI-H28 and a breast cancer cell line MDA-MB-231 was found to have reduced the cellular growth, plating efficiency, and anchorage-independent growth. The tumorigenicity of these cancer cell lines as determined by subcutaneous inoculation in nude mice was similarly suppressed by TGFBI expression. Likewise, TGFBI expression reduced the proportion of S-phase while increased the proportion of G1 phase in these cells. The redistribution of cell cycle phase after re-expression of TGFBI was correspondent with transiently elevated expression of p21 and p53. The activities of senescence-associated β-galactosidase and telomerase were enhanced in TGFBI-transfected cells.ConclusionCollectively, these results imply that TGFBI plays a suppressive role in the development of mesothelioma and breast cancer cells, possibly through inhibitions of cell proliferation, delaying of G1-S phase transition, and induction of senescence.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.