Elucidation of the roles of the two ARID3B isoforms in both cisplatin-sensitive and resistant ovarian cancer cell lines

Ovarian cancer is the leading cause of death from a gynecological malignancy in the United States, yet the genetic mechanisms that contribute to ovarian cancer progression are poorly understood.  We have determined that ARID3B, a member of the AT-rich interaction domain (ARID) family of proteins, is overexpressed in ovarian cancer.  Therefore, we want to assess if ARID3B plays an important role in ovarian cancer progression. We have demonstrated that there are two ARID3B isoforms: the long form (ARID3BFL at 61kDa) and the short form (ARID3Bsh at 28kDa). ARID3BFL binds DNA and induces apoptosis in ovarian cancer cell lines while ARID3Bsh does not induce cell death. We show that the ARID3BFL is mostly found in the nucleus and some is found in the membrane of cells in ovarian cancer cells lines (OVCA) 429 and 433. Furthermore, the short isoform of ARID3B (when overexpressed) is primarily found in cytoplasmic and membrane/mitochondria fractions. However, cisplatin-resistant ovarian cancer cell lines (A2780cis) exhibit a 50% decrease in the mRNA for both isoforms compared to the cisplatin sensitive parental A2780 cells. Furthermore there is increased punctate nuclear accumulation of ARID3B in the A2780cis cells compared to the A2780 cells. Therefore, we hypothesize that reducing ARID3B concentration in ovarian cancer cells may contribute to cisplatin resistance. Further elucidation of the roles of the two ARID3B isoforms in both cisplatin sensitive and resistant cancer cell lines will help us understand ovarian cancer progression, cellular response to chemotherapy, and develop prognostic markers and targeted therapies.