Low SP1 Expression Differentially Affects Intestinal-Type Compared with Diffuse-Type Gastric Adenocarcinoma

Hun Seok Lee, Cheol Keun Park, Ensel Oh, Özgür Cem Erkin, Hun Soon Jung, Mi Hyun Cho, Mi Jeong Kwon, Seoung Wan Chae, Seok Hyung Kim, Li Hui Wang, Min Jeong Park, Su Yeon Lee, Ho Bin Yang, Lina Jia, Yoon La Choi, Young Kee Shin

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Specificity protein 1 (SP1) is an essential transcription factor that regulates multiple cancer-related genes. Because aberrant expression of SP1 is related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. Although patient survival decreased as SP1 expression increased (P<0.05) in diffuse-type gastric cancer, the lack of SP1 expression in intestinal-type gastric cancer was significantly correlated with poor survival (P<0.05). The knockdown of SP1 in a high SP1-expressing intestinal-type gastric cell line, MKN28, increased migration and invasion but decreased proliferation. Microarray data in SP1 siRNA-transfected MKN28 revealed that the genes inhibiting migration were downregulated, whereas the genes negatively facilitating proliferation were increased. However, both migration and invasion were decreased by forced SP1 expression in a low SP1-expressing intestinal-type gastric cell line, AGS. Unlike the intestinal-type, in a high SP1-expressing diffuse-type gastric cell line, SNU484, migration and invasion were decreased by SP1 siRNA. In contrast to previous studies that did not identify differences between the 2 histological types, our results reveal that low expression of SP1 is involved in cancer progression and metastasis and differentially affects intestinal-type compared with diffuse-type gastric adenocarcinoma.

Original languageEnglish
Article numbere55522
JournalPLoS ONE
Volume8
Issue number2
DOIs
StatePublished - 20 Feb 2013

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