Role of STAT3 as a negative regulator in Mac2- binding protein expression.
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.
Park
Yuk Pheel
YP
Stem cell Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Kim
Jong-Tae
JT
Yang
Young
Y
Lim
Jong Seok
JS
Yoon
Do Young
DY
Kim
Jong Wan
JW
Lee
Hee Gu
HG
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D014162:Transfection
D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C114782:TAA90K protein, human; D004815:Epidermal Growth Factor; D019098:Telomerase