Role of STAT3 as a negative regulator in Mac2-binding protein expression

Yuk Pheel Park, Jong Tae Kim, Young Yang, Jong Seok Lim, Do Young Yoon, Jong Wan Kim, Hee Gu Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalKorean Journal of Laboratory Medicine
Volume28
Issue number3
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • EGF
  • hTERT
  • Mac-2BP
  • STAT3

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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