Triple-negative breast cancer (TNBC) refers to any breast cancer that lacks of estrogen receptor (ER), progesterone receptors (PE) and HER2 protein. It accounts for approximately 15%-25% of all the breast cancers and characterized with the poorest prognosis. So far, no targeted therapies like Tamoxifen or Herceptin have been developed to help prevent recurrence in women with TNBC. Standard treatment is still surgery with adjuvant chemotherapy and radiotherapy.

Krüppel-like factor 5 (KLF5) transcription factor highly expresses in a subset of ER-negative breast cancers. It promotes breast cancer cell cycle progression, survival, and tumorigenesis, but the mechanism by which KLF5 promotes breast cancer is still to be understood. In a most recent study of Dr. CHEN Ceshi’s research team (Kunming Institute of Zoology, CAS), first evidence of mPGES1 as a new target gene has been provided, making it a new biomarker and potential therapeutic target for TNBC.

In general, it has been accepted that KLF5 is an oncogene and execute functions by regulating downstream target genes. Higher KLF5 expression always associates with a short survival time in breast cancer patients. In the previous study (2006) of Dr. CHEN, mPGES1 has been identified as one of KLF5’s target genes by microarray analysis. mPGES1 mediates the prostaglandin E2 (PGE2) synthesis and cell proliferation by acting with cyclooxygenase-2 (COX-2). As a bioactive lipid that can regulate a wide range of biological effects associated with inflammation and cancer, PGE2 has long been implicated in promoting tumor cell growth and invasion via angiogenesis. So, either COX-2 or mPGES1 have been considered as important potential targets in breast cancer.

In the present study, Dr. CHEN’s team has provided several lines of evidence supporting the expression and functional coupling between KLF5 and mPGES1. Their analysis showed that KLF5 directly binds to the mPGES1 proximal promoter, activating its transcription and then regulating its mRNA and protein expression in multiple breast cell lines. Functionally, both KLF5 and mPGES1 similarly promote PGE2 synthesis and breast cell proliferation. Meanwhile, an immunohistochemistry (IHC) study in primary breast tumors also demonstrated that the expression of mPGES1 is positively associated with negative ER/PR/HER2 status.

This study provided first evidence and rationale for developing mPGES1 as a breast cancer diagnosis biomarker and therapeutic target. More details could be obtained by the Journal of Biological Chemistry (http://www.jbc.org/content/early/2013/08/02/jbc.M113.483958.long).