The neurofibromatosis type 2 (NF2) tumor suppressor gene encodes a cytoskeletal/membranous protein, Merlin. Inactivation of the NF2 gene is known to cause tumors of the nervous system in humans and multiple cancers in mice. Although Merlin's role as a tumor suppressor has been well studied in other systems, its function in breast cancer is unknown.

In this study, we have determined that the expression of Merlin protein is decreased in breast cancer tissues. Concomitantly, we observed increased expression of osteopontin (OPN), a malignancy-promoting protein that induces activation of Akt phosphorylation. Thus, there is an inverse correlation between the expression of Merlin and OPN in breast cancer. Ectopic restoration of Merlin in breast cancer cells significantly reduced attributes of malignant behavior as assessed in vitro by foci formation, soft agar colony formation, and invasion. In vivo, breast cancer cells stably expressing Merlin displayed reduced tumor growth and progression in athymic mice. Further, our investigations reveal that OPN-initiated activation of Akt signaling results in phosphorylation of Merlin at Serine 315 that targets it for proteasome-mediated degradation.

Thus, our studies elucidate the utility of Merlin as an important biomarker in breast cancer and also identify a novel mechanism for the loss of Merlin expression in breast cancer. Moreover, our studies demonstrate the ability of Merlin to act as a tumor suppressor in breast cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1012. doi:10.1158/1538-7445.AM2011-1012