Mac-2 결합단백질 발현에서의 STAT3의 역할 = Role of STAT3 as a Negative Regulator in Mac2- Binding Protein Expression

다국어 초록 (Multilingual 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. (Korean
J Lab Med 2008;28:230-8)

다국어 초록 (Multilingual 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. (Korean
J Lab Med 2008;28:230-8)

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