Ovarian cancer (OC) is the most common and deadliest gynecologic malignancies in the United States, with an estimated 21,290 new cases and 14,180 deaths in 2015. Therefore, it is highly imperative to identify novel molecular targets driving OC progression, so that an effective treatment strategy can be developed against this devastating disease. In the present study, we investigated the role of MYB in OC pathogenesis. MYB/c-MYB is a cellular progenitor of v-MYB oncogenes, which encodes for a transcription factor, and confers its oncogenic activity by regulating the expression of several target genes. First, we examined the expression of MYB in clinical specimens and OC cell lines by immunohistochemical and immunoblot analysis, respectively. We observed intense staining of MYB in the tissues of all the subtypes of OC, while no or negligible staining was observed in normal ovarian tissues. Moreover, we found MYB to be expressed in all the OC cell lines examined, with its heightened expression in highly aggressive (TOV112D, SKOV3-ip) and chemo-resistant (A2780-Cip) OC cell lines. To examine the pathological significance of MYB in OC, we silenced its expression in TOV112D, SKOV3-ip and A2780-Cip OC cell lines. Functional studies demonstrate that silencing of MYB led to decrease in growth and clonogenic ability in TOV112D, SKOV3-ip and A2780-Cip cells, as compared to their scrambled sequence-transfected (Scr) control cells. Furthermore, MYB-silencing reduced motility and invasion, as well as resulted in the loss of mesenchymal and gain of epithelial markers. In addition, our data showed that TOV112D-shMYB, SKOV3-ip-shMYB and A2780-Cip-shMYB were more sensitive to cisplatin-cytotoxicity as compared to their respective controls. Altogether, our studies provide the first experimental evidence for a functional role of MYB in altered growth, malignant behavior and chemoresistance of ovarian cancer.
Citation Format: Sanjeev Kumar Srivastava, Seema Singh, Arun Bhardwaj, James E. Carter, Rodney P. Rocconi, Jennifer Scalici, Ajay P. Singh. Multiple functional implications of MYB in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1989.