Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?

Breast cancer is the leading cause of cancer death among women in worldwide and France. The disease prognosis and treatment differ from one breast cancer subtype to another, and the disease outcome depends on many prognostic factors. Deregulation of ion flux (especially Ca 2+ flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IP 3 R) is a major player in the regulation of the Ca 2+ flux from the endoplasmic reticulum to the cytoplasm. The IP 3 Rs (and particularly the IP 3 R3 subtype) are known to be involved in proliferation, migration, and invasion processes in breast cancer cell lines. The objective of the present study was to evaluate the potential value of IP 3 Rs as prognostic biomarkers in breast cancer. We found that expression levels of IP 3 R3 and IP 3 R1 (but not IP 3 R2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IP 3 R3 subtype was expressed more strongly than the IP 3 R1 and IP 3 R2 subtypes. Furthermore, the expression of IP 3 R3 (but not of IP 3 R1 or IP 3 R2) was positively correlated with prognostic factors such as tumor size, regional node invasion, histologic grade, proliferation index, and hormone receptor status. In an analysis of public databases, we found that all IP 3 Rs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IP 3 R subtypes, IP 3 R3 expression is upregulated in breast cancer and is correlated with prognostic factors.