Open Access

Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway

  • Authors: Gengyun Wen, Mei Hong, Bingyan Li, Wupeng Liao, Simon K. Cheng, Burong Hu, Gloria M. Calaf, Ping Lu, Michael A. Partridge, Jian Tong, Tom K. Hei
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  • Published online on: Thursday, June 23, 2011
  • Pages: 1001-1009
  • DOI: 10.3892/ijo.2011.1097

Abstract

As an uncommon cancer, mesothelioma is very hard to treat with a low average survival rate owing to its usual late detection and being highly invasive. The link between asbestos exposure and the development of mesothelioma in humans is unequivocal. TGFBI, a secreted protein that is induced by transforming growth factor-β in various human cell types, has been shown to be associated with tumorigenesis in various types of tumors. It has been demonstrated that TGFBI expression is markedly suppressed in asbestos-induced tumorigenic cells, while an ectopic expression of TGFBI significantly suppresses tumorigenicity and progression in human bronchial epithelial cells. In order to delineate a potential role of TGFBI in mediating the molecular events that occur in mesothelioma tumorigenesis, we generated stable TGFBI knockdown mutants from the mesothelium cell line Met-5A by using an shRNA approach, and secondly created ectopic TGFBI overexpression mutants from the mesothelioma cell line H28 in which TGFBI is absent. We observed that in the absence of TGFBI, the knockdown mesothelial and mesothelioma cell lines exhibited an elevated proliferation rate, enhanced plating efficiency, increased anchorage-independent growth, as well as an increased cellular protein synthesis rate as compared with their respective controls. Furthermore, cell cycle regulatory proteins c-myc/cyclin D1/phosphor-Rb were upregulated; a more active PI3K/Akt/mTOR signaling pathway was also detected in TGFBI-depleted cell lines. These findings suggest that TGFBI may repress mesothelioma tumorigenesis and progression via the PI3K/Akt signaling pathway.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Wen, G., Hong, M., Li, B., Liao, W., Cheng, S., Hu, B., Calaf, G., Lu, P., Partridge, M., Tong, J., & Hei, T. (2011). Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway. International Journal of Oncology, 39(4), 1001-1009.
MLA
Wen, Hong, Li, Liao, Cheng, Hu, Calaf, Lu, Partridge, Tong, and Tom Hei. "Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway." International Journal of Oncology International Journal of Oncology 39.4 (2011): 1001-1009.
Chicago
Wen, Hong, Li, Liao, Cheng, Hu, Calaf, Lu, Partridge, Tong, and Tom Hei. "Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 1001-1009.