Transcriptional regulation of human osteopontin promoter by C/EBPα and AML-1 in metastatic cancer cells

Yan Nien Liu, Bean Bu Kang, J. H. Chen

研究成果: 雜誌貢獻文章同行評審

31 引文 斯高帕斯(Scopus)

摘要

Osteopontin (OPN) is a secreted glycoprotein produced by osteoclasts, macrophages, T cells, hematopoietic cells, and vascular smooth muscle cells. It contributes to macrophage homing and cellular immunity. It also mediates neovascularization, inhibits apoptosis, and plays important roles in extracellular matrix remodeling and angiogenesis. These properties are also characteristics of metastatic cancer cells. Consequently, the OPN gene was found to be upregulated among various metastatic cancer cells. This suggests that OPN is involved in tumor metastasis. How the OPN gene is upregulated in metastatic cancer cells remains to be illustrated. Thus, we investigated the transcriptional activation of the OPN promoter in the human metastatic cancer cell line A2058. We cloned the OPN promoter, and serial deletion analysis of the OPN promoter showed that the region between -170 and -127 may act as an enhancer to control the OPN gene in metastatic tumor cells. This region was found to contain overlapped AML-1 and C/EBP binding site motifs. Gel-mobility-shift assays using the A2058 nuclear extract and AML-1a or C/EBPα (CCAAT/ enhancer binding protein alpha) recombinant protein indicated that these two transcription factors can bind to the overlapped AML-1 /C/EBP binding site motifs on the OPN regulatory sequence from -147 to -127. Surprisingly, the gel-shift experiments did not show supershift complex formation between AML-1 and C/EBPα. Functional analysis showed that the C/EBPα was more potent than the complex of AML-1 and its cofactor CBFβ to upregulate the OPN promoter. In addition, AML-1 and C/EBPα did not exhibit transactivation additively or synergistically. Our results suggest that AML-1 and C/ EBPα play an important role in the upregulation of the OPN gene in metastatic tumor cells.
原文英語
頁(從 - 到)278-288
頁數11
期刊Oncogene
23
發行號1
DOIs
出版狀態已發佈 - 一月 8 2004
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 遺傳學
  • 癌症研究

指紋

深入研究「Transcriptional regulation of human osteopontin promoter by C/EBPα and AML-1 in metastatic cancer cells」主題。共同形成了獨特的指紋。

引用此