Carcinogenesis Advance Access originally published online on December 19, 2005
Carcinogenesis 2006 27(5):936-944; doi:10.1093/carcin/bgi316
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Overexpression of thymosin ß-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively
Institute of Pharmacology, College of Medicine, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan, R.O.China, 1 Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.China and 2 Institute of Biopharmaceutical Science, Collage of Life Science, National Yang-Ming University, Taipei, Taiwan, R.O.China
* To whom correspondence should be addressed. Email: yeusu{at}ym.edu.tw
The present work was conducted to further examine the effects of thymosin ß-4 (Tß4) upregulation on the apoptosis of SW480 colon cancer cells induced by T cells and various chemotherapeutic agents because reduced susceptibility to the cytotoxicity of an anti-Fas IgM (CH-11) in Tß4-overexpressing cells has previously been reported by us. As expected, Tß4 overexpressers were also more resistant to the killing effect of FasL-bearing Jurkat T cells. On the other hand, pretreating these cells with an MMP inhibitor restored not only their Fas levels but also their sensitivity to CH-11, suggesting a pivotal role of MMP in downregulating Fas in Tß4 overexpressers. Interestingly, while the susceptibilities of Tß4 overexpressers to 5-FU and irinotecan remained unchanged, they were more resistant to doxorubicin and etoposide which triggered apoptosis via a mitochondrial pathway. Concordantly, activation of both caspases 9 and 3 in Tß4 overexpressers by the two aforementioned topoisomerase II inhibitors was dramatically abrogated which could be accounted mainly by an increased expression of Survivin, a critical anti-apoptotic factor. Finally, poor survival was found in stage III colon cancer patients whose tumors were stained positively by the anti-Survivin antibody. Thus, advantages such as immune evasion and resistance to anticancer drug-induced apoptosis acquired by colon cancer cells through Tß4 overexpression might facilitate their survival during metastasis and chemotherapy.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
K. Iguchi, M. Ito, S. Usui, A. Mizokami, M. Namiki, and K. Hirano Downregulation of Thymosin {beta}4 Expression by Androgen in Prostate Cancer LNCaP Cells J Androl, March 1, 2008; 29(2): 207 - 212. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H.-C. Ho, C.-H. Chuang, C.-Y. Ho, Y.-R. V. Shih, O. K.-S. Lee, and Y. Su Internalization Is Essential for the Antiapoptotic Effects of Exogenous Thymosin {beta}-4 on Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 27 - 33. [Abstract] [Full Text] [PDF] |
||||

