Transcription factor TFII-I causes transcriptional upregulation of GRP78 synthesis in prostate cancer cells
✍ Scribed by U.K. Misra; F. Wang; S.V. Pizzo
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 277 KB
- Volume
- 106
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Receptor‐recognized forms of α~2~‐macroglobulin (α~2~M*) bind to cell surface‐associated GRP78 and induce proliferative and survival signaling in prostate cancer cells. As part of the cellular response to α~2~M*, GRP78 expression is itself upregulated. In response to other stimuli, the transcription factor TFII‐I upregulates GRP78 by binding to its gene promoter. We have, therefore, studied the role of TFII‐I in transcriptional upregulation of GRP78 in 1‐LN human prostate cancer cells stimulated with α~2~M*. This treatment caused a two‐ to threefold increase in TFII‐I and GRP78 synthesis from [^35^S]‐labeled precursor amino acids. Synthesis of both TFII‐I and GRP78 were significantly reduced by silencing TFII‐I gene expression or pretreatment of cells with genistein or actinomycin D. Confocal microscopy was employed to demonstrate relocation of TFII‐I to the nucleus. In α~2~M*‐stimulated cells, moreover, TFII‐I bound to the GRP78 promoter as determined by CHIP assay. We also demonstrate binding of TFII‐I to the c‐fos promoter, consistent with its role in upregulating c‐fos gene expression. In non‐lymphoid cells, phosphorylated c‐Src is an activator of TFII‐I. Ligation of GRP78 on 1‐LN cells with α~2~M* was followed by tyrosine phosphorylation of c‐Src as well as TFII‐I. We conclude that α~2~M*‐induced increase in GRP78 synthesis is caused by transcriptional upregulation of TFII‐I which binds to the GRP78 promoter and thus potentiates its cell survival and antipoptotic functions in 1‐LN prostate cancer cells. J. Cell. Biochem. 106: 381–389, 2009. © 2008 Wiley‐Liss, Inc.