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Title: Differences in transcriptional effects of 1 alpha,25 dihydroxyvitamin D3 on fibroblasts associated to breast carcinomas and from paired normal breast tissues
Authors: CAMPOS, Laura TojeiroBRENTANI, HelenaROELA, Rosimeire AparecidaKATAYAMA, Maria Lucia HirataLIMA, LeandroROLIM, Cintia FloresMILANI, CintiaFOLGUEIRA, Maria Aparecida Azevedo KoikeBRENTANI, Maria Mitzi
Abstract: The effects of 1 alpha,25 dihydroxyvitamin D3 (1,25D) on breast carcinoma associated fibroblasts (CAFs) are still unknown. This study aimed to identify genes whose expression was altered after 1,25D treatment in CAFs and matched adjacent normal mammary associated fibroblasts (NAFs). CAFs and NAFs (from 5 patients) were cultured with or without (control) 1,25D 100 nM. Both CAF and NAF expressed vitamin D receptor (VDR) and 1,25D induction of the genomic pathway was detected through up-regulation of the target gene CYP24A1. Microarray analysis showed that despite presenting 50% of overlapping genes, CAFs and NAFs exhibited distinct transcriptional profiles after 1,25D treatment (FDR <0.05). Functional analysis revealed that in CAFs, genes associated with proliferation (NRG1, WNT5A, PDGFC) were down regulated and those involved in immune modulation (NFKBIA, TREM-1) were up regulated, consistent with anti tumor activities of 1,25D in breast cancer. In NAFs, a distinct subset of genes was induced by 1,25D, involved in anti apoptosis, detoxification, antibacterial defense system and protection against oxidative stress, which may limit carcinogenesis. Co-expression network and interactome analysis of genes commonly regulated by 1,25D in NAFs and CAFs revealed differences in their co-expression values, suggesting that 1,25D effects in NAFs are distinct from those triggered in CAFs.
Appears in Collections:Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - FM/MPS
Artigos e Materiais de Revistas Científicas - HC/InRad
Artigos e Materiais de Revistas Científicas - LIM/21
Artigos e Materiais de Revistas Científicas - LIM/24

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