Antiviral signaling protein MITA acts as a tumor suppressor in breast cancer by regulating NF-κB induced cell death

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Bhatelia, Khyati¹  Singh, Aru²  Tomar, Dhanendra¹  Singh, Kritarth¹  Sripada, Lakshmi¹  Chagtoo, Megha²  Prajapati, Paresh¹  Singh, Rochika¹  Godbole, Madan M.²  Singh, Rajesh³ 

[1] Indian Inst Adv Res, Sch Biol Sci & Biotechnol, Dept Cell Biol, Gandhinagar, India

[2] Sanjay Gandhi Postgrad Inst Med Sci, Dept Endocrinol, Lucknow 226014, Uttar Pradesh, India

[3] Maharaja Sayajirao Univ Baroda, Dept Biochem, Vadodara 390005, Gujarat, India

关键词: MITA;    Tumor suppressor gene;    NF-kappa B;    Breast cancer;   

DOI  :  10.1016/j.bbadis.2013.11.006

来源: Elsevier

【 摘 要 】

Emerging evidences suggest that chronic inflammation is one of the major causes of tumorigenesis. The role of inflammation in regulation of breast cancer progression is not well established. Recently Mediator of IRF3 Activation (MITA) protein has been identified that regulates NF-kappa B and IFN pathways. Role of MITA in the context of inflammation and cancer progression has not been investigated. In the current report, we studied the role of MITA in the regulation of cross talk between cell death and inflammation in breast cancer cells. The expression of MITA was significantly lower on in estrogen receptor (ER) positive breast cancer cells than ER negative cells. Similarly, it was significantly down regulated in tumor tissue as compared to the normal tissue. The overexpression of MITA in MCF-7 and T47D decreases the cell proliferation and increases the cell death by activation of caspases. MITA positively regulates NF-kappa B transcription factor, which is essential for MITA induced cell death. The activation of NF-kappa B induces TNF-alpha production which further sensitizes MITA induced cell death by activation of death receptor pathway through capsase-8. MITA expression decreases the colony forming units and migration ability of MCF-7 cells. Thus, our finding suggests that MITA acts as a tumor suppressor which is down regulated during tumorigenesis providing survival advantage to tumor cell. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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