Abstract A05: Identification of RASA1 as a novel melanoma tumor suppressor gene

In this study, we addressed functional roles of RASA1 in melanoma tumorigenesis. Ectopic expression of wild-type RASA1 in human melanoma cell lines SKMEL28 and WM983C (with BRAF V600E) decreased, while RASA1 Y472H mutant enhanced soft agar colony formation, tumor growth, and Ras activity. The RASA1 L481F mutant lost its tumor suppressive activity. The siRNA- or shRNA-mediated knockdown of RASA1 promoted soft agar colony formation, tumor growth, and RAS activation in human melanoma cell lines IGR1 and KML1 (with BRAFV600E). Mechanistically, RASA1 required RasGAP activity to suppress colony formation and showed higher activity toward R-Ras isoform among Ras superfamily of small GTPases. To determine RASA1 level in melanocytic lesions, immunohistochemical analysis of RASA1 on human melanoma tissue microarray (TMA) was performed. RASA1 expression was frequently down-regulated in metastatic melanoma samples (11.4% (4/35) of lymph node metastasis and 3.4% (1/29) of distal metastases) compared to primary melanomas (33.3% (21/63)) and dysplastic nevi (44.1% (15/34)). Thus, these data support that RASA1 is a novel melanoma tumor suppressor that is inactivated by loss of expression or by mutation.Citation Format: Hyeran Sung, Krishna L. Kanchi, Jane Messina, Ji-Hyun Lee, Li Ding, Richard K. Wilson, Jeffrey S. Weber, Minjung Kim. Identification of RASA1 as a novel melanoma tumor suppressor gene. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Bio...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Advances in Melanoma Biology Source Type: research