HMGA2 mediates topoisomerase II inhibitors cytotoxicity in breast cancer cells

2110 Background: The HMGA2 protein belongs to the architectural transcription factor HMGA family, which plays a role in chromosomal organization and transcriptional regulation. Ectopic overexpression of HMGA2 is known to be associated with neoplastic transformation in several human tumors. Clinically, HMGA2 expression in patients with breast cancer is an indicator for poor prognosis and metastasis. However, the precise role and molecular events mediated by HMGA2 in tumorigenesis and its relation to chemotherapy resistance still need to be defined. Methods: Pa-4 and HMGA2-expressing Pa-4/HMGA2 cells, 2 breast cancer cells (both ER and PR negative) with differential expression of HMGA2, HS578T and HCC1419 were used to test their sensitivity towards doxorubicin (DOX) and irinotecan (CPT11) in a dose-dependent manner. HS578T cells express higher endogenous level of HMGA2 than HCC1419. Results: Both DOX and CPT11-treatments was able to inhibit Pa-4 and Pa-4/HMGA2 cells in a dose-dependent fashion. Notably, DOX...