Role of STAT3 as a Negative Regulator in Mac2- Binding Protein Expression / 대한진단검사의학회지
The Korean Journal of Laboratory Medicine
; : 230-238, 2008.
Article
in En
| WPRIM
| ID: wpr-206226
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Membrane Glycoproteins
/
Transfection
/
Down-Regulation
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Cell Line
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Telomerase
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RNA, Small Interfering
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Cell Line, Tumor
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Epidermal Growth Factor
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STAT3 Transcription Factor
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Antigens, Neoplasm
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
The Korean Journal of Laboratory Medicine
Year:
2008
Type:
Article