Role of STAT3 as a negative regulator in Mac2-binding protein expression
- Authors
- Park, Yuk Pheel; Kim, Jong-Tae; Yang, Young; Lim, Jong Seok; Yoon, Do Young; Kim, Jong Wan; Lee, Hee Gu
- Issue Date
- Jun-2008
- Publisher
- 대한진단검사의학회
- Keywords
- Mac-2BP; Stat3; EGF; hTERT
- Citation
- Annals of Laboratory Medicine, v.28, no.3, pp 230 - 238
- Pages
- 9
- Journal Title
- Annals of Laboratory Medicine
- Volume
- 28
- Number
- 3
- Start Page
- 230
- End Page
- 238
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14256
- DOI
- 10.3343/kjlm.2008.28.3.230
- ISSN
- 2234-3806
2234-3814
- 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.
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