Abstract 412: SEC11A contributes to malignant progression through promotion of EGF and TGF-α secretion in gastric cancer.

Abstract

Abstract Gastric cancer (GC) is one of the most common human cancers. We previously performed Serial Analysis of Gene Expression (SAGE) on four primary GCs and identified several GC-specific genes. In the present study, we have built an in-house oligonucleotide array on which 394 genes selected based on our SAGE data and previously reported array data to allow for the study of the genes that are most relevant to gastric carcinogenesis. We focused on the SEC11A gene, which encodes SPC18 protein. SPC18 is one of the member of signal peptidase complex. SPC18 mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in GC tissue samples. Expression and distribution of SPC18 protein was investigated by immunohistochemistry in two independent GC cohorts (Hiroshima cohort, n = 99 and Chiba cohort, n = 989). To determine the effect of SPC18 on cell growth and invasiveness in vitro, MTT and Boyden chamber invasion assays were performed. To evaluate the influence of SPC18 on cell growth in vivo, GC cells were injected into SCID mice. The levels of TGF-α and EGF in media from the GC cells were measured by ELISA. Overexpression of SEC11A mRNA was observed in 40% of GC cases by qRT-PCR. Immunohistochemical analysis of SPC18 revealed that 26% of GC cases were positive for SPC18 in Hiroshima cohort and 20% of GC cases were positive for SPC18 in Chiba cohort. SPC18-positive GC cases showed poorer survival than SPC18-negative GC cases in both Hiroshima cohort and Chiba cohort by Kaplan-Meier analysis. Forced expression of SPC18 activates GC cell growth in vitro and in vivo. The levels of TGF-α and EGF in culture media from GC cells were reduced by knockdown of SPC18. These results indicate that SPC18 contributes to malignant progression through promotion of EGF and TGF-α secretion in GC. Citation Format: Naohide Oue, Tetsutaro Hayashi, Reiko Ito, Akiko Nagatsuma, Kazuhiro Sentani, Naoya Sakamoto, Katsuhiro Anami, Naohiro Uraoka, Yutaka Naito, Kazuyoshi Yanagihara, Atsushi Ochiai, Hiroki Sasaki, Wataru Yasui. SEC11A contributes to malignant progression through promotion of EGF and TGF-α secretion in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 412. doi:10.1158/1538-7445.AM2013-412