title: NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.
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.
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Leonardo K
authors.initials: LK
authors.lastname: Teixeira
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Nina
authors.initials: N
authors.lastname: Carrossini
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Sécca
authors.affiliation: b Brain Institute, Federal University of Rio Grande do Norte (UFRN) , Natal , Brazil.
authors.forename: José E
authors.initials: JE
authors.lastname: Kroll
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Déborah C
authors.initials: DC
authors.lastname: DaCunha
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faget
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: Lilian D S
authors.initials: LD
authors.lastname: Carvalho
authors.affiliation: b Brain Institute, Federal University of Rio Grande do Norte (UFRN) , Natal , Brazil.
authors.forename: Sandro J
authors.initials: SJ
authors.lastname: de Souza
authors.affiliation: a Program of Cellular Biology , Brazilian National Cancer Institute (INCA) , Rio de Janeiro , Brazil.
authors.forename: João P B
authors.initials: JP
authors.lastname: Viola
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D016466:CHO Cells; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D019927:Cyclin E; D006801:Humans; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D019927:Cyclin E; D050778:NFATC Transcription Factors
keywords: B lymphocytes; NFAT; Tumor; cell cycle; cyclin E