Literature DB >> 27399331

NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.

Leonardo K Teixeira1, Nina Carrossini1, Cristiane Sécca1, José E Kroll2, Déborah C DaCunha1, Douglas V Faget1, Lilian D S Carvalho1, Sandro J de Souza2, João P B Viola1.   

Abstract

The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

Entities:  

Keywords:  B lymphocytes; NFAT; Tumor; cell cycle; cyclin E

Mesh:

Substances:

Year:  2016        PMID: 27399331      PMCID: PMC5004684          DOI: 10.1080/15384101.2016.1203485

Source DB:  PubMed          Journal:  Cell Cycle        ISSN: 1551-4005            Impact factor:   4.534


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