Recent data suggest that chemokines could be essential players in breast carcinogenesis. We previously showed that the CXC chemokine CXCL8 (interleukin-8) was overexpressed in estrogen receptor a (ERa)-negative breast cell lines. Analysis of CXCL8 chromosomal location showed that several CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL4V1, CXCL5, CXCL6, CXCL7, and CXCL8) were localized in the same narrow region (360 kb in size) of chromosome 4. We thus hypothesized that they could belong to the same cluster. Quantification of these chemokines in breast tumors showed that samples expressing high CXCL8 also produced elevated levels of CXCL1, CXCL3, and CXCL5, and displayed low content of ERa. CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8 were co-regulated both in tumors and in breast cancer cell lines. CXCL5 and CXCL8 were mainly produced by epithelial cells, whereas CXCL1, CXCL2, and CXCL3 had a high expression in blood cells. The overexpression of these chemokines in tumor cells was not the result of gene amplification, but rather of an enhanced gene transcription. Our data suggest that high CXCL8 expression in tumors is mainly correlated to activating protein-1 (AP-1) pathway and to a minor extent to NF-kB pathway. Interestingly, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL8 chemokines were present at higher levels in metastases when compared with grade I and III biopsies. High levels of CXCL8, CXCL1, and CXCL3 accounted for a shorter relapse-free survival of ERa-positive patients treated with tamoxifen. In summary, we present evidences that multiple CXC chemokines are co-expressed in CXCL8-positive breast tumors. In addition, these chemokines could account for the higher aggressiveness of these types of tumors.

Despite years of intensive research, breast cancer remains a major cause of death among women. New strategies to combat breast cancer are being developed, one of the most exciting of which is the use of chemopreventive agents. Resveratrol (RES) is a polyphenolic compound found in plants that seems to have a wide spectrum of biological activity. RES has been shown to afford protection against several types of cancer. This review summarizes the chemopreventive effects of RES at the three major stages of breast carcinogenesis: initiation, promotion, and progression. It has anti-oxidant and anti-inflammatory properties, and may induce apoptosis as well as modulate cell cycle and estrogen receptor function in breast cancer cell lines. Although RES has shown remarkable promise as a potent chemopreventive agent in breast cancer, further studies are needed to etablish its usefulness.

Bisphenol A were removed from consumer products and replaced by chemical substitutes such as Bisphenol S (BPS). Based on their structural similarity, BPS may be obesogen like Bisphenol A in mice. Our objective was to determine the impact of BPS on lipid homeostasis in C57Bl/6 mice after perinatal and chronic exposure. Pregnant mice were exposed to BPS via the drinking water (0.2; 1.5; 50μg/kg bw/d). Treatment began at gestational day 0 and continued in offspring up to 23-weeks old. Then, offspring mice were fed with a standard or high fat diet. The body weight, food consumption, fat mass and energy expenditure were measured. A lipid load test was performed to check the postprandial triglyceridemia. Plasma parameters and mRNA gene expression in adipose tissues were also analysed. BPS induced overweight in male mice offspring fed with a HFD at the two highest doses. There was no change in food intake and energy expenditure. The overweight was correlated to the fat mass, hyperinsulinemia and hyperleptinemia. The plasma triglyceride clearance was significantly increased with BPS and tyloxapol(®) (triglyceride clearance inhibitor) reversed this phenomenon. BPS induced alteration in mRNA expression of marker genes involved in adipose tissue homeostasis: hormone sensitive lipase, PPARγ, insulin receptor, SOCS3 and adiponectin. This is the first time that BPS is described as obesogenic at low doses and after perinatal and chronic exposure in male mice. BPS potentiated the obesity induced by a HFD by inducing the lipid storage linked to faster lipid plasma clearance.