Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/40393
標題: Modification of Alternative Splicing of Mcl-1 Pre-mRNA Using Antisense Morpholino Oligonucleotides Induces Apoptosis in Basal Cell Carcinoma Cells
作者: Shieh, J.J.
謝政哲
Liu, K.T.
Huang, S.W.
Chen, Y.J.
Hsieh, T.Y.
關鍵字: up-regulation
bcl-2 family
death
expression
cancer
differentiation
pathways
survival
domain
member
期刊/報告no:: Journal of Investigative Dermatology, Volume 129, Issue 10, Page(s) 2497-2506.
摘要: Myeloid cell leukemia-1 (Mcl-1, Mcl-1L) is an anti-apoptotic protein of the Bcl-2 family that acts as a critical molecule in apoptosis control. Mcl-1 pre-mRNA can undergo alternative splicing to yield the short isoform, Mcl-1S, which resembles BH3-only pro-apoptotic proteins and induces apoptosis. Overexpression of Mcl-1 may play a role in various human tumors, and Mcl-1 may serve as a target in cancer therapy. In this study, we found an imbalance between the expression levels of Mcl-1L and Mcl-1S in the skin basal cell carcinoma (BCC) cell line when compared with primary keratinocytes. We showed that overexpression of Mcl-1S induces apoptosis in BCC cells. Finally, we showed that Mcl-1 antisense morpholino oligonucleotides (AMOs) can specifically target Mcl-1 pre-mRNA and shift the splicing pattern from Mcl-1L to Mcl-1S mRNA and protein. This shift increases the level of pro-apoptotic Mcl-1S and reduces the level of anti-apoptotic Mcl-1L, which induces apoptosis in BCC cells and AGS cells, a human gastric adenocarcinoma epithelial cell line. Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis.
URI: http://hdl.handle.net/11455/40393
ISSN: 0022-202X
文章連結: http://dx.doi.org/10.1038/jid.2009.83
Appears in Collections:生物醫學研究所

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