SFRP1 is an important negative regulator of the WNT pathway in human breast cancer.
SFRP1 is an important molecule of the WNT pathway. We were one of the first research group to characterize an SFRP1-specific antibody and showed that SFRP1 protein is completely or almost completely lost in more than 80% of all breast carcinomas (Klopocki et al.: Abstract*). In this project we could further show that loss of SFRP1 occurs early in breast cancer development: Tissue of patients with ductal carcinoma in situ (DCIS) already shows similarly high rates of SFRP1 loss as invasive ductal breast carcinoma (IDC).
Our research group was the first to describe that SFRP1 is a class II tumor suppressor gene (C2TSG) in human breast cancer (Veeck et al.: Abstract*). In the course of tumor development, aberrant methylation of cytosine residues often occurs in the promoter region of tumor suppressor genes. This promoter DNA methylation leads to gene being switched off ("silenced”). We found this epigenetic change in the SFRP1 promoter region in 61% of breast cancer patients analyzed (n=130) and we could show that it is responsible for the transcriptional loss of SFRP1. Beyond that, no gene inactivating mutations were found so that aberrant SFRP1 promoter methylation appears to be the fundamental molecular mechanism of SFRP1 gene silencing in breast cancer. Interestingly, SFRP1 promoter methylation was significantly associated with a shortened overall survival of patients (Veeck et al.: Abstract*).