Abstract LB-112: SP1 suppression is associated with poor prognosis in intestinal-type gastric adenocarcinoma

Abstract

Specificity protein 1 (SP1) is a DNA-binding protein that activates and regulates the transcription of multiple genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric cancer and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). Multivariate analysis demonstrated that SP1 downregulation is an independent negative prognostic factor in intestinal-type gastric cancer. When SP1 downreguation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion was increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS was decreased by SP1 induction. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that weak SP1 expression is involved in cancer progression and metastasis, and leads to poor prognosis in intestinal-type gastric adenocarcinoma. 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 LB-112. doi:10.1158/1538-7445.AM2011-LB-112