Role of STAT3 as a Negative Regulator in Mac2- Binding Protein Expression.
10.3343/kjlm.2008.28.3.230
- Author:
Yuk Pheel PARK
1
;
Jong Tae KIM
;
Young YANG
;
Jong Seok LIM
;
Do Young YOON
;
Jong Wan KIM
;
Hee Gu LEE
Author Information
1. Stem cell Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea. hglee@kribb.re.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Mac-2BP;
STAT3;
EGF;
hTERT
- MeSH:
Antigens, Neoplasm/genetics/*metabolism;
Cell Line;
Cell Line, Tumor;
Down-Regulation;
Epidermal Growth Factor/metabolism;
Humans;
Membrane Glycoproteins/genetics/*metabolism;
RNA, Small Interfering;
STAT3 Transcription Factor/genetics/*metabolism;
Telomerase/metabolism;
Transfection
- From:The Korean Journal of Laboratory Medicine
2008;28(3):230-238
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Mac-2 binding protein (Mac-2BP) is a secreted glycoprotein from the culture fluid of several human cancer cells, especially breast, lung, and gastric cells. Mac-2BP plays a role in immune response and cell adhesion activity in patients with various cancer and infectious diseases. In this study, we attempted to identify the regulators of Mac-2BP expression at the transcriptional level. METHODS: To determine the effect of epidermal growth factor (EGF) to Mac-2BP expression in gastric cancers, we constructed the different lengths of Mac-2BP promoter plasmids and measured the promoter activity and Mac-2BP expression. In addition to investigating the role of signal transducer and activator of transcription3 (STAT3) or human telomerase reverse transcriptase (hTERT) as a regulator of Mac-2BP, we transfected the small interfering RNA (siRNA) specific for STAT3 or hTERT, and Mac-2BP level was observed by a quantitative ELISA. RESULTS: EGF treatment could suppress the Mac-2BP transcription in HEK293 or gastric cancer cell lines (SNU-638 or AGS). In 5'-deleted promoter experiment, pGL3-Mac Pro-2377 transfected cells showed a decreased luciferase activity compared to pGL3-Mac Pro-2277. We also identified that (-2,366/-2,356) on Mac-2BP promoter is a putative STAT3 binding site and suppression of STAT3 with STAT3 specific siRNA increased the Mac-2BP level, suggesting the role of STAT3 as a negative regulator, in contrast to hTERT, which is known as a positive regulator. CONCLUSIONS: EGF signal is critical for the Mac-2BP expression, and more importantly, STAT3 could work as a negative regulator, while hTERT as a positive regulator in Mac-2BP transcription.
