Abstract
p73, a new p53 family member, is a transcription factor that is increasingly recognized in cancer research as an important player in tumorigenesis as well as in chemotherapeutic drug sensitivity. Despite the substantial structural and functional similarities to p53, accumulating evidence suggests that p53 and p73 may differently regulate their transcriptional targets. In this study, we have investigated the role of p73 in regulation of the gastrin gene promoter. Gastrin is a peptide hormone and an important factor in determining the progression of a number of human malignancies. Our results show that p73 can bind to the gastrin promoter. This leads to transcriptional upregulation of gastrin mRNA. We also found that the levels of gastrin and p73 transcripts correlate in primary gastric tumors. Taken together, our results demonstrate a novel mechanism for regulation of gastrin gene transcription and support a concept that p53 and p73 may have different biological roles in tumors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aly A, Shulkes A, Baldwin GS . (2001). Int J Cancer 94: 307–313.
Aly A, Shulkes A, Baldwin GS . (2004). Biochim Biophys Acta 1704: 1–10.
Baldwin GS, Hollande F, Yang Z, Karelina Y, Paterson A, Strang R et al. (2001). J Biol Chem 276: 7791–7796.
Benard J, Douc-Rasy S, Ahomadegbe JC . (2003). Hum Mutat 21: 182–191.
Brown D, Yallampalli U, Owlia A, Singh P . (2003). Endocrinology 144: 201–211.
Caplin M, Savage K, Khan K, Brett B, Rode J, Varro A et al. (2000). Br J Surg 87: 1035–1040.
Ciccotosto GD, McLeish A, Hardy KJ, Shulkes A . (1995). Gastroenterology 109: 1142–1153.
Cobb S, Wood T, Ceci J, Varro A, Velasco M, Singh P . (2004). Cancer 100: 1311–1323.
Daulhac L, Kowalski-Chauvel A, Pradayrol L, Vaysse N, Seva C . (1999). J Biol Chem 274: 20657–20663.
Finley GG, Koski RA, Melhem MF, Pipas JM, Meisler AI . (1993). Cancer Res 53: 2919–2926.
Fox JG, Wang TC, Rogers AB, Poutahidis T, Ge Z, Taylor N et al (2003). Gastroenterology 124: 1879–1890.
Goetze JP, Nielsen FC, Burcharth F, Rehfeld JF . (2000). Cancer 88: 2487–2494.
Guan M, Peng HX, Yu B, Lu Y . (2003). Jpn J Clin Oncol 33: 215–220.
Han S, Semba S, Abe T, Makino N, Furukawa T, Fukushige S et al. (1999). Eur J Surg Oncol 25: 194–198.
Hansen OH, Pedersen T, Larsen JK, Rehfeld JF . (1976). Gut 17: 536–541.
Irwin MS, Kondo K, Marin MC, Cheng LS, Hahn WC, Kaelin Jr WG . (2003). Cancer Cell 3: 403–410.
Kang MJ, Park BJ, Byun DS, Park JI, Kim HJ, Park JH et al. (2000). Clin Cancer Res 6: 1767–1771.
Kochman ML, DelValle J, Dickinson CJ, Boland CR . (1992). Biochem Biophys Res Commun 189: 1165–1169.
Koh TJ, Bulitta CJ, Fleming JV, Dockray GJ, Varro A, Wang TC . (2000). J Clin Invest 106: 533–539.
Koh TJ, Dockray GJ, Varro A, Cahill RJ, Dangler CA, Fox JG et al. (1999). J Clin Invest 103: 1119–1126.
Koh TJ, Field JK, Varro A, Liloglou T, Fielding P, Cui G et al. (2004). Cancer Res 64: 196–201.
Liu L, Cui X, Sakaguchi T, Sasaki M, Suda T, Hatakeyama K . (2001). J Int Med Res 29: 297–303.
Moll UM, Erster S, Zaika A . (2001). Biochim Biophys Acta 1552: 47–59.
Ng SW, Yiu GK, Liu Y, Huang LW, Palnati M, Jun SH et al. (2000). Oncogene 19: 1885–1890.
Nimura Y, Mihara M, Ichimiya S, Sakiyama S, Seki N, Ohira M et al. (1998). Int J Cancer 78: 437–440.
Pilozzi E, Talerico C, Platt A, Fidler C, Ruco L . (2003). Mol Pathol 56: 60–62.
Seva C, Dickinson CJ, Yamada T . (1994). Science 265: 410–412.
Seva C, Kowalski-Chauvel A, Blanchet JS, Vaysse N, Pradayrol L . (1996). FEBS Lett 378: 74–78.
Singh P, Lu X, Cobb S, Miller BT, Tarasova N, Varro A et al. (2003). Am J Physiol Gastrointest Liver Physiol 284: G328–G339.
Singh P, Velasco M, Given R, Varro A, Wang TC . (2000). Gastroenterology 119: 162–171.
Stiewe T, Tuve S, Peter M, Tannapfel A, Elmaagacli AH, Putzer BM . (2004). Clin Cancer Res 10: 626–633.
Sun XF . (2002). Clin Cancer Res 8: 165–170.
Tannapfel A, Schmelzer S, Benicke M, Klimpfinger M, Kohlhaw K, Mossner J et al. (2001). J Pathol 195: 163–170.
Tannapfel A, Wasner M, Krause K, Geissler F, Katalinic A, Hauss J et al. (1999). J Natl Cancer Inst 91: 1154–1158.
Tokuchi Y, Hashimoto T, Kobayashi Y, Hayashi M, Nishida K, Hayashi S et al. (1999). Br J Cancer 80: 1623–1629.
Tomkova K, Belkhiri A, El-Rifai W, Zaika AI . (2004). Cancer Res 64: 6390–6393.
Wang TC, Dangler CA, Chen D, Goldenring JR, Koh T, Raychowdhury R et al. (2000). Gastroenterology 118: 36–47.
Wang TC, Koh TJ, Varro A, Cahill RJ, Dangler CA, Fox JG et al. (1996). J Clin Invest 98: 1918–1929.
Weber A, Bellmann U, Bootz F, Wittekind C, Tannapfel A . (2002). Int J Cancer 99: 22–28.
Zaika AI, Kovalev S, Marchenko ND, Moll UM . (1999). Cancer Res 59: 3257–3263.
Zaika AI, Slade N, Erster SH, Sansome C, Joseph TW, Pearl M et al. (2002). J Exp Med 196: 765–780.
Acknowledgements
This work was supported by the National Institutes of Health Grant (NIH CA-108956).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tomkova, K., El-Rifai, W., Vilgelm, A. et al. The gastrin gene promoter is regulated by p73 isoforms in tumor cells. Oncogene 25, 6032–6036 (2006). https://doi.org/10.1038/sj.onc.1209610
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209610
Keywords
This article is cited by
-
ΔNp73α regulates MDR1 expression by inhibiting p53 function
Oncogene (2008)