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Vitamin D Analogs in Cancer Prevention and Therapy pp 111–122Cite as

Squamous Cell Carcinomas Fail to Respond to the Prodifferentiating Actions of 1,25(OH)2D3: Why?

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Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 164))

Abstract

1,25(OH)2D3regulates a number of cellular events which contribute to its ability to stimulate differentiation of the keratinocyte. 1,25(OH)2D3raises the intracellular calcium (Cai) level in part by increasing the expression of the calcium receptor (CaR). This sensitizes the cell to extracellular calcium, triggering the signaling pathway coupled to the CaR, which results in a rise in Cai.1,25(OH)2D3induces the family of phospholipases C (PLC). These enzymes mediate the hydrolysis of phosphatidyl inositol bisphosphate (PIP2) to form inositol tris phosphate (IP3) and diacylglycerol (DG), which stimulate calcium release from intracellular stores and activate protein kinases C (PKC), respectively. The CaR and other G protein coupled receptors signal through PLC-b, whereas tyrosine kinase growth factor receptors such s the EGF receptor signal through PLC-g. Calcium and PKC regulate the expression of genes in part by controlling the levels and activity of AP-1 transcription factors.1,25(OH)2D3also directly induces structural genes such as involucrin, a substrate for transglutaminase, which crosslinks it to other substrates to form the cornified envelope. 1,25(OH)2D3regulates gene expression by activating the vitamin D receptor (VDR), a transcription factor, which, in ombination with the retinoid X receptor (RXR) or retinoid A receptor (RAR), binds to its vitamin D response elements (VDRE) in the promoters of genes whose expression it regulates.

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Author information

Authors and Affiliations

  1. Veterans Affairs Medical Center (111 N), University of California, 4150 Clement Street, San Francisco, CA, 94121, USA

    Daniel D. Bikle

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  1. Daniel D. Bikle
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  2. Zhongjian Xie
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  3. Dean Ng
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  4. Chia-Ling Tu
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  5. Yuko Oda
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Editors and Affiliations

  1. Hautklinik und Poliklinik der Universitätskliniken des Saarlandes, Kirrberger Str., 66421, Homburg/Saar

    Jörg Reichrath  & Wolfgang Tilgen  & 

  2. Frauenklinik des Universitätsklinikums der Eberhard-Karls-Universität, Calwerstr. 7, 71076, Tübingen

    Michael Friedrich

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© 2003 Springer-Verlag Berlin Heidelberg

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Bikle, D.D., Xie, Z., Ng, D., Tu, CL., Oda, Y. (2003). Squamous Cell Carcinomas Fail to Respond to the Prodifferentiating Actions of 1,25(OH)2D3: Why?. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_7

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  • DOI: https://doi.org/10.1007/978-3-642-55580-0_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62435-3

  • Online ISBN: 978-3-642-55580-0

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