S100A8/A9 is associated with estrogen receptor loss in breast cancer

Abstract

Abstract. S100A8 and S100A9 are calcium-binding proteins that are secreted primarily by granulocytes and monocytes, and are upregulated during the inflammatory response. S100A8 and S100A9 have been identified to be expressed by epithelial cells involved in malignancy. In the present study, the transcriptional levels of S100A8 and S100A9 were investigated in various subtypes of breast cancer (BC), and the correlation with estrogen receptor 1 (ESR1) and GATA binding protein 3 (GATA3) gene expression was evaluated using microarray datasets. The expression of S100A8 and S100A9 in BC cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The regulation of ESR1 and GATA3 by administration of recombinant S100A8/A9 was examined in the BC MCF-7 cell line using quantitative (q)PCR. The association between S100A8 and S100A9 and overall survival (OS) was investigated in GeneChip ® data of BC. The expression levels of S100A8 and S100A9 were higher in human epidermal growth factor receptor 2 (Her2)-amplified and basal-like BC. The messenger (m)RNA levels of S100A8 and S100A9 were inversely correlated with ESR1 and GATA3 expression. S100A8/A9 induced a 10-fold decrease in the mRNA levels of ESR1 in MCF-7 cells. Poor OS was associated with high expression levels of S100A9, but not with high expression levels of S100A8 in BC. In conclusion, strong expression and secretion of S100A8/A9 may be associated with the loss of estrogen receptor in BC, and may be involved in the poor prognosis of Her2 + /basal-like subtypes of BC.

HRD1 sensitizes breast cancer cells to Tamoxifen by promoting S100A8 degradation

“…S100A8 plays an important role in chemotherapy resistance and metastasis of breast cancer [3, 6]. In the present study, we found that HRD1 downregulated S100A8 expression.…”

“…It is reported that, S100A8 is associated with estrogen receptor loss in breast cancer [3]. Furthermore, S100A8 is involved in the chemistry-drug resistance in lots of kind of tumors.…”

ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer

“…HYOU1 is a hypoxiainduced protein and its upregulation suppresses programmed cell death, contributing to invasiveness in breast cancer [34]. S100A9 has been identi ed to be expressed by epithelial cells involved in malignancy and its expression levels are inversely correlated with ERα in breast cancer [35]. CDC42EP2 is a member of the binder of Rho GTPases (Borg) family and little is known about its role in the disease [36].…”

“…For example, NFAT5 is regulated by an estrogen-induced microRNA [37] and the regulation is mediated via PI3K/AKT-signaling pathways [38]. In addition, A100A9, a calcium-binding protein that is highly expressed in malignant breast cancer, induces a decrease of ERα in MCF-7 cell [35], and inhibits PI3K/AKT pathway in pancreatic adenocarcinoma cells [39]. Collectively, the current study proposes that ELOVL2 is an integral signaling molecule of the AKT axis in ER-positive breast cancer cells.…”

Utility of Different Immunohistochemical Stain for Diagnosis of Invasive Breast Cancer

“…It is known that abnormal expression of multiple S100 proteins is associated with breast cancer, including S100A2, S100A4, S100A6, S100A7, S100A8, S100A9, and S100A11 [21]. Increasing studies have reported S100A8 is overexpression in lung cancer and breast cancer [22,23], and it is associated with the progress, matastasis and chemo-resistance in breast cancer [24][25][26]. In this study, we will use immunohistochemical stain to detect the different expression of Jab1 and S100A8 in invasive breast carcinoma and para-carcinoma tissues and show the correlationship of these two markers and clinical characteristics.…”