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Background  Inflammation is a major player in breast cancer (BC) progression. Allograft-inflammatory factor-1 (AIF1) is a crucial mediator in the inflammatory response. AIF1 reportedly plays a role in BC, but the mechanism remains to be elucidated. We identified two AIF1 isoforms, AIF1v1 and AIF1v3, which were differentially expressed between affected and unaffected sisters from families with high risk of BC with no deleterious BRCA1/BRCA2 mutations (BRCAX). We investigated potential functions of AIFv1/v3 in BC of varying severity and breast adipose tissue by evaluating their expression, and association with metabolic and clinical parameters of BC patients.    Methods  AIF1v1/v3 expression was determined in BC tissues and cell lines using quantitative real-time PCR. Potential roles and mechanisms were examined in the microenvironment (fibroblasts, adipose tissue, monocytes and macrophages), inflammatory response (cell reaction in BC subgroups), and metabolism [treatment with docosahexaenoic acid (DHA)]. Association of AIF1 transcript expression with clinical factors was determined by Spearman’s rank correlation. Bioinformatics analyses were performed to characterize transcripts.    Results   AIF1v1/v3  were mostly expressed in the less severe BC samples, and their expression appeared to originate from the tumor microenvironment.  AIF1  isoforms had different expression rates and sources in breast adipose tissue; lymphocytes mostly expressed  AIF1v1  while activated macrophages mainly expressed  AIF1v3 . Bioinformatics analysis revealed major structural differences suggesting distinct functions in BC progression. Lymphocytes were the most infiltrating cells in breast tumors and their number correlated with  AIF1v1  adipose expression. Furthermore, DHA supplementation significantly lowered the expression of  AIF1  isoforms in BRCAX cell lines. Finally, the expression of  AIF1  isoforms in BC and breast adipose tissue correlated with clinical parameters of BC patients.    Conclusions  Results strongly suggest that AIF1v1 as much as AIF1v3 play a major role in the crosstalk between BC and infiltrating immune cells mediating tumor progression, implying their high potential as target molecules for BC diagnostic, prognostication and treatment.    Electronic supplementary material  The online version of this article (10.1186/s12935-018-0663-3) contains supplementary material, which is available to authorized users.

An isoform of AIF1 involved in breast cancer