NAC1, a BTB/POZ protein overexpressed in uterine sarcomas

Abstract

Background: The purpose of this study was to investigate the role of Nucleus accumbens-associated 1 (NAC1) in the development of uterine sarcomas.

Materials and methods: NAC1 expression and localization in the normal myometrium, benign leiomyoma, and uterine sarcoma were assessed with immunohistochemistry. NAC1-specific siRNA was used to inactivate NAC1 for in vitro biological assays.

Results: Almost all cases of uterine sarcoma were found to overexpress NAC1. Expression of NAC1 was significantly higher in uterine sarcomas than in benign leiomyomas (p<0.0001). NAC1 gene knockdown inhibited cell growth and induced apoptosis in SKN, a leiomyosarcoma cell line, and in OMC-9, an endometrial stromal sarcoma cell line, both of which overexpress NAC1.

Conclusion: Uterine sarcomas with NAC1 overexpression are clinically the most aggressive, chemoresistant, and radioresistant tumors. Therefore, detection of NAC1 overexpression in uterine sarcomas may identify patients who will benefit from NAC1-targeted therapy.