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1α,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells

Oncogene volume 24, pages 6533–6544 (2005)Cite this article

Abstract

1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) has antitumor activity in addition to its classical action on calcium metabolism and bone tissue biology. It is thought to regulate the expression of multiple target genes and thus modulate processes critical for tumor growth and metastases. Here we show that 1α,25(OH)2D3 differentially regulates the expression of Id1 and Id2 genes, members of a family of transcriptional regulators of cell proliferation and differentiation. 1α,25(OH)2D3 induced epithelial differentiation in SW480-ADH human colon carcinoma cell line by promoting expression of the proteins implicated in adherent junction formation, including E-cadherin, and by inhibiting β-catenin transcriptional activity. 1α,25(OH)2D3 activated the human Id1 gene promoter and rapidly induced Id1 RNA and protein. Ectopic overexpression of Id1 was not sufficient to induce E-cadherin, which was critical for the morphological changes induced by 1α,25(OH)2D3 in SW480-ADH cells. Conversely, Id2 transcription rate, RNA and protein levels were decreased by 1α,25(OH)2D3. Id2 downregulation by 1α,25(OH)2D3 mediated the antiproliferative effect of 1α,25(OH)2D3 on SW480-ADH cells. In addition, we showed that 1α,25(OH)2D3 changed the levels of the inducer of angiogenesis, vascular endothelial growth factor and the potent antiangiogenic factor thrombospondin-1, leading to a balanced change in the angiogenic potential of SW480-ADH human colon carcinoma cells.

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References

  • Behrens J . (2000). Ann. N.Y. Acad. Sci., 910, 21–33; discussion 33–35.

  • Benezra R, Rafii S and Lyden D . (2001). Oncogene, 20, 8334–8341.

  • Bernardi RJ, Johnson CS, Modzelewski RA and Trump DL . (2002). Endocrinology, 143, 2508–2514.

  • Chomczynski P and Sacchi N . (1987). Anal. Biochem., 162, 156–159.

  • Church GM and Gilbert W . (1984). Proc. Natl. Acad. Sci. USA, 81, 1991–1995.

  • Dalhoff K, Dancey J, Astrup L, Skovsgaard T, Hamberg KJ, Lofts FJ, Rosmorduc O, Erlinger S, Bach Hansen J, Steward WP, Skov T, Burcharth F and Evans TR . (2003). Br. J. Cancer, 89, 252–257.

  • Dameron KM, Volpert OV, Tainsky MA and Bouck N . (1994). Science, 265, 1582–1584.

  • Diaz GD, Paraskeva C, Thomas MG, Binderup L and Hague A . (2000). Cancer Res., 60, 2304–2312.

  • Evans SR, Shchepotin EI, Young H, Rochon J, Uskokovic M and Shchepotin IB . (2000). Int. J. Oncol., 16, 1249–1254.

  • Ezura Y, Tournay O, Nifuji A and Noda M . (1997). J. Biol. Chem., 272, 29865–29872.

  • Gross C, Stamey T, Hancock S and Feldman D . (1998). J. Urol., 159, 2035–2039; discussion 2039–2040.

  • Gulliford T, English J, Colston KW, Menday P, Moller S and Coombes RC . (1998). Br. J. Cancer, 78, 6–13.

  • Gumireddy K, Ikegaki N, Phillips PC, Sutton LN and Reddy CD . (2003). Biochem. Pharmacol., 65, 1943–1955.

  • Guyton KZ, Kensler TW and Posner GH . (2001). Annu. Rev. Pharmacol. Toxicol., 41, 421–442.

  • Halline AG, Davidson NO, Skarosi SF, Sitrin MD, Tietze C, Alpers DH and Brasitus TA . (1994). Endocrinology, 134, 1710–1717.

  • Hewitt RE, McMarlin A, Kleiner D, Wersto R, Martin P, Tsokos M, Stamp GW, Stetler-Stevenson WG and Tsoskas M . (2000). J. Pathol., 192, 446–454.

  • Iseki K, Tatsuta M, Uehara H, Iishi H, Yano H, Sakai N and Ishiguro S . (1999). Int. J. Cancer, 81, 730–733.

  • Israel MA, Hernandez MC, Florio M, Andres-Barquin PJ, Mantani A, Carter JH and Julin CM . (1999). Cancer Res., 59, 1726s–1730s.

  • Jensen SS, Madsen MW, Lukas J, Binderup L and Bartek J . (2001). Mol. Endocrinol., 15, 1370–1380.

  • Koli K and Keski-Oja J . (2000). Cell Growth Differ., 11, 221–229.

  • Lasorella A, Boldrini R, Dominici C, Donfrancesco A, Yokota Y, Inserra A and Iavarone A . (2002). Cancer Res., 62, 301–306.

  • Lasorella A, Iavarone A and Israel MA . (1996). Mol. Cell. Biol., 16, 2570–2578.

  • Lasorella A, Noseda M, Beyna M, Yokota Y and Iavarone A . (2000). Nature, 407, 592–598.

  • Lasorella A, Uo T and Iavarone A . (2001). Oncogene, 20, 8326–8333.

  • Leibovitz A, Stinson JC, McCombs III WB, McCoy CE, Mazur KC and Mabry ND . (1976). Cancer Res., 36, 4562–4569.

  • Liu Y, Encinas M, Comella JX, Aldea M and Gallego C . (2004). Mol. Cell. Biol., 24, 2662–2672.

  • Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K and Benezra R . (1999). Nature, 401, 670–677.

  • Mantell DJ, Owens PE, Bundred NJ, Mawer EB and Canfield AE . (2000). Circ. Res., 87, 214–220.

  • Matsumura ME, Lobe DR and McNamara CA . (2002). J. Biol. Chem., 277, 7293–7297.

  • Nehlin JO, Hara E, Kuo WL, Collins C and Campisi J . (1997). Biochem. Biophys. Res. Commun., 231, 628–634.

  • Nishii Y and Okano T . (2001). Steroids, 66, 137–146.

  • Palmer HG, Gonzalez-Sancho JM, Espada J, Berciano MT, Puig I, Baulida J, Quintanilla M, Cano A, de Herreros AG, Lafarga M and Munoz A . (2001). J. Cell Biol., 154, 369–387.

  • Palmer HG, Sanchez-Carbayo M, Ordonez-Moran P, Larriba MJ, Cordon-Cardo C and Munoz A . (2003). Cancer Res., 63, 7799–7806.

  • Ramsauer M and D'Amore PA . (2002). J. Clin. Invest., 110, 1615–1617.

  • Rockman SP, Currie SA, Ciavarella M, Vincan E, Dow C, Thomas RJ and Phillips WA . (2001). J. Biol. Chem., 276, 45113–45119.

  • Ruzinova MB, Schoer RA, Gerald W, Egan JE, Pandolfi PP, Rafii S, Manova K, Mittal V and Benezra R . (2003). Cancer Cell, 4, 277–289.

  • Scaglione-Sewell BA, Bissonnette M, Skarosi S, Abraham C and Brasitus TA . (2000). Endocrinology, 141, 3931–3939.

  • Schlaeppi JM, Gutzwiller S, Finkenzeller G and Fournier B . (1997). Endocr. Res., 23, 213–229.

  • Sikder HA, Devlin MK, Dunlap S, Ryu B and Alani RM . (2003). Cancer Cell, 3, 525–530.

  • Smith DC, Johnson CS, Freeman CC, Muindi J, Wilson JW and Trump DL . (1999). Clin. Cancer Res., 5, 1339–1345.

  • Vennstrom B and Bishop JM . (1982). Cell, 28, 135–143.

  • Verlinden L, Verstuyf A, Convents R, Marcelis S, Van Camp M and Bouillon R . (1998). Mol. Cell. Endocrinol., 142, 57–65.

  • Volpert OV, Pili R, Sikder HA, Nelius T, Zaichuk T, Morris C, Shiflett CB, Devlin MK, Conant K and Alani RM . (2002). Cancer Cell, 2, 473–483.

  • Wilson JW, Deed RW, Inoue T, Balzi M, Becciolini A, Faraoni P, Potten CS and Norton JD . (2001). Cancer Res., 61, 8803–8810.

  • Woo PL, Cercek A, Desprez PY and Firestone GL . (2000). J. Biol. Chem., 275, 28649–28658.

  • Yam CH, Fung TK and Poon RY . (2002). Cell Mol. Life Sci., 59, 1317–1326.

  • Yokota Y . (2001). Oncogene, 20, 8290–8298.

  • Zebedee Z and Hara E . (2001). Oncogene, 20, 8317–8325.

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Acknowledgements

We acknowledge with gratitude all researchers who contributed the reagents: J Campisi for Id1 promoter, E Hara for pGEXId1A, JD Norton for pcDNA3-Id2, AG Herreros for E-cadherin promoter constructs, A Alfranca for VEGF promoter and A Bernad for pLZR-iresEGFP, I Palmero for anti-p21 antibody, C Cales for anti-cyclin A antibody. We specially acknowledge C Cales, M Campanero and I Palmero for their advice in cell cycle. This work was supported by grants SAF-2001-1349 and SAF-2004-04152 from Ministerio de Ciencia y Tecnología to B Jimenez, SAF2004-01015 to A Munoz and SAF-2004-07717 to M del Rio. NI Fernandez and M Garcia has been supported by a Comunidad Autonoma de Madrid fellowship.

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Authors and Affiliations

  1. Instituto de Investigaciones Biomedicas CSIC-UAM, Madrid, Spain

    Nuria Isabel Fernandez-Garcia, Alicia Gonzalez-Martin, Alberto Muñoz & Benilde Jimenez

  2. Department of Biochemistry, Universidad Autonoma de Madrid, Madrid, Spain

    Nuria Isabel Fernandez-Garcia, Alicia Gonzalez-Martin & Benilde Jimenez

  3. Cancer Research, London, WC2A 3PX, UK

    Hector G Palmer

  4. Project on Damage, Repair and Tissue Engineering CIEMAT, Madrid, Spain

    Marta Garcia & Marcela del Rio

  5. Instituto de Biomedicina de Valencia CSIC, Valencia, Spain

    Domingo Barettino

  6. Department of Urology, Northwestern University Medical School, Chicago, IL, USA

    Olga Volpert

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  1. Nuria Isabel Fernandez-Garcia
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Correspondence to Benilde Jimenez.

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Fernandez-Garcia, N., Palmer, H., Garcia, M. et al. 1α,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells. Oncogene 24, 6533–6544 (2005). https://doi.org/10.1038/sj.onc.1208801

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