Expression and significance of CHIP in canine mammary gland tumors

CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that caninduce ubiquitination and degradation of several oncogenic proteins. The expression ofCHIP is frequently lower in human breast cancer than in normal breast tissue. However, theexpression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. Weinvestigated the potential correlation between CHIP expression and mammary gland tumorprognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistryand real-time RT-PCR. CHIP protein expression was significantly correlated with thehistopathological diagnosis, outcome of disease and tumor classification. Thetranscriptional level of CHIP was significantly higher in normal tissues(P=0.001) and benign tumors (P=0.009) than it inmalignant tumors. CHIP protein expression was significantly correlated with thetranscriptional level of CHIP (P=0.0102). The log-ranktest survival curves indicated that patients with low expression of CHIP had shorteroverall periods of survival than those with higher CHIP protein expression(P=0.050). Our data suggest that CHIP may play an important role in theformation and development of CMGTs and serve as a valuable prognostic marker and potentialtarget for genetic therapy.