Post-Transcriptional Regulation of Proto-Oncogene c-fms in Breast Cancer

In the development and progression of breast cancers, both the c-fms proto-oncogene (which encodes the tyrosine kinase receptor for CSF-1) as well as CSF-1 (colony stimulating factor1), play an important role. Evidence from transgenic models suggests that c-fms encodes for the sole receptor for CSF-1 (Dai et al, 2002). We and others have found that c-fms and/or CSF1 are expressed by the tumor epithelium in several human epithelial cancers (Kacinski et al, 1988, 1990, 1991; Rettenmier et al, 1989; Filderman et al, 1992; Ide et al, 2002); elevated levels of c-fms and CSF-1 are associated with poor prognosis (Kacinski et al, 1988; Tang et al, 1990; Price et al, 1993; Chambers et al, 1997, 2009; Scholl et al, 1993; Kluger et al, 2004; Sapi 2004). In human breast cancer, 94% of in situ and invasive lesions express c-fms (Kacinski et al, 1991; Flick et al, 1997), while 36% express both CSF-1 and c-fms (Kacinski et al, 1991; Scholl et al, 1993). Among breast cancer patients, serum levels of CSF-1 are frequently elevated in those with metastases (Kacinski et al, 1991). In breast tumors, nuclear CSF-1 staining is associated with poor survival (Scholl et al, 1994), and c-fms expression confers an increased risk for local relapse (Maher et al, 1998). In a large breast cancer tissue array, c-fms (Kluger et al, 2004) is strongly associated with lymph node metastasis, and poor survival. This strong correlation with prognosis suggests an etiologic role for c-fms/CSF-1 in tumor invasion and metastasis.