RT-PCR Analysis of TopBP1 Gene Expression in Hereditary Breast Cancer

Ewa Forma; Magdalena Bernaciak; Hanna Romanowicz-Makowska; Magdalena Bryś

doi:10.2478/v10107-009-0006-1

Authors

Ewa Forma University of Łódź, Department of Cytobiochemistry
Magdalena Bernaciak University of Łódź, Department of Cytobiochemistry
Hanna Romanowicz-Makowska Polish Mother’s Memorial Hospital, Research Institute, Department of Clinical Pathomorphology
Magdalena Bryś University of Łódź, Department of Cytobiochemistry

DOI:

https://doi.org/10.2478/v10107-009-0006-1

Keywords:

TopBP1, gene expression, RT-PCR, hereditary breast cancer

Abstract

Hereditary predisposition to breast cancer determined in large part by loss of function mutations in one of two genes BRCA1 and BRCA2. Besides BRCA1 and BRCA2 other genes are also likely to be involved in hereditary predisposition to breast cancer. TopBP1 protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Expression of TopBP1 gene at the mRNA level was analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 94 samples of hereditary breast cancer. Analysis of TopBP1 mRNA level showed that expression of TopBP1 is significantly downregulated in poorly differentiated breast cancer (grade III according Bloom-Richardson system (P<0.05).

Downloads

Download data is not yet available.

References

Boner, W., Taylor, E.R., Tsirimonaki, E., Yamane, K., Campo, M.S., Morgan, I.M. 2002. A functional interaction between the human papillomavirus 16 transcription/replication factor E2 and the DNA damage response protein TopBP1. J. Biol. Chem. 277: 22297–22303.
Google Scholar

Burrows, A.E., Elledge, S. 2008. How ATR turns on: TopBP1 goes on ATRIP with ATR. Genes Dev. 22: 1416–1421.
Google Scholar

Cimprich, K.A., Cortez, D. 2008. ATR: an essential regulator of genome integrity. Nature Rev. Mol. Cell Biol. 9: 616–627.
Google Scholar

Delacroix, S., Wagner, J.M., Kobayashi, M., Yamamoto, K.I., Karnitz, L.M. 2007. The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev. 21: 1472–1477.
Google Scholar

Donaldson, M.M., Boner, W., Morgan, I.M. 2007. TopBP1 regulates human papillomavirus type 16 E2 interaction with chromatin. J. Virol. 81: 4338–4342.
Google Scholar

Easton, D.F. 1999. How many more breast cancer predisposition genes are there? Breast Cancer Res. 1: 14–17.
Google Scholar

Herold, S., Wanzel, M., Beuger, V., Frohme, C., Beul, D., Hillukkala, T., Syvaoja, J., Saluz, H.P., Haenel, F., Eilers, M. 2002. Negative regulation of the mammalian UV response by Myc through association with Miz-1. Mol. Cell 10: 509–521.
Google Scholar

Ho, G.H., Calvano, J.E., Bisogna, M., Van Zee, K.J. 2001. Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas. Breast Cancer Res. Treat. 69: 115–122.
Google Scholar

Jeon, Y., Lee, K.Y., Ko, M.J., Lee, Y.S., Kang, S., Hwang. D.S. 2007. Human TopBP1 participates in cyclinE/CDK2 activation and preinitiation complex assembly during G1/S transition. J. Biol. Chem. 282: 14882–14890.
Google Scholar

Karppinen, S.M., Erkko, H., Reini, K., Pospiech, H., Heikkinen, K., Rapakko, K., Syvaoja, J.E., Winqvist, R. 2006. Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer. Eur. J. Cancer. 42: 2647–2652.
Google Scholar

Kim, J.E., Mcavoy, S.A., Smith, D.I., Chen, J. 2005. Human TopBP1 ensures genome integrity during normal S phase. Mol. Cel. Biol. 25: 10907–10915.
Google Scholar

Kumagai, A., Lee, J., Yoo, H.Y., Dunphy, W.G. 2006. TopBP1 activates the ATR-ATRIP complex. Cell 124: 943–955.
Google Scholar

Kwon, M.J., Nam, E.S., Cho, S.J., Park, H.R., Shin, H.S., Park, J.H., Park, C.H., Lee, W.J. 2009. E2F1 expression predicts outcome in Korean women who undergo surgery for breast cancer. Ann. Surg. Oncol. 17: 564–571.
Google Scholar

Lee, J., Kumagai, A., Dunphy, W.G. 2007. The Rad9-Hus1-Rad-1 checkpoint clamp regulates interaction of TopBP1 with ATR. J. Biol. Chem. 282: 28036–28044.
Google Scholar

Liu, K., Lin, F.T., Ruppert, J.M., Lin, W.C. 2003. Regulation of E2F1 by BRCT domain-containing protein TopBP1. Mol. Cell. Biol. 23: 3287–3304.
Google Scholar

Liu, K., Luo, Y., Lin, F.T., Lin, W.C. 2004. TopBP1 recruits BRG1/BRM to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. Genes Dev. 21: 1472–1477.
Google Scholar

Liu, K., Paik, J.C., Wang, B., Lin, F.T., Lin. W.C. 2006 Regulation of TopBP1 oligomerization by Akt/PKB for cell survival. EMBO J. 25: 4795–4807.
Google Scholar

Liu, K., Bellam, N., Lin, H.Y., Wang, B., Stockard, C.R., Geizzle, W.E., Lin, W.C. 2009. Regulation of p53 by TopBP1: a potential mechanism for p53 inactivation in cancer. Mol. Cell. Biol. 29: 2673–2693.
Google Scholar

Lu, K., Kauff, N., Powell, B., Chen, L.M., Cass, I., Lancaster, J. 2009. Hereditary breast and ovarian syndrome, ACOG Practice Bull. Gynecol. Oncol. 113: 6–11.
Google Scholar

Makiniemi, M., Hillukkala, T., Tuusa, J., Reini, K., Vaara, M., Huang, D., Pospiech, H., Majuri, I., Westerling, T., Mäkelä, T.P., Syväoja, J.E. 2001. BRCT domain-containing protein TopBP1 functions in DNA replication and damage response. J. Biol. Chem. 276: 30099–30406.
Google Scholar

Morishima, K.I., Sakamoto, S., Kobayashi, J., Izumi, H., Suda, T., Matsumoto, Y., Tauchi, H., Ide, H., Komatsu, K., Matsuura, S. 2007. TopBP1 associates with NBS1 and is involved in homologous recombination repair, Biochem. Biophys. Res. Commun. 362: 872–879.
Google Scholar

Perera, D., Perez-Hidalgo, L., Moens, P.B., Reini, K., Lakin, N., Syväoja, J.E., San-Segundo, P.A., Freire, R. 2004. TopBp1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint, Mol. Biol. Cell 15: 1568–1579.
Google Scholar

Reini, K., Uitto, L., Perera, D., Moens, P.B., Freire, R., Syväoja, J.E. 2004. TopBP1 localises to centrosomes in mitosis and chromosome cores in meiosis, Chromosoma 112: 323–330.
Google Scholar

Schmidt, U., Wollmann, Y., Franke, C., Grosse, F., Saluz, H.P., Hanel, F. 2008. Characterization of the interaction between the human DNA topoisomerase IIβ-binding protein 1 (TopBP1) and the cell division cycle protein 45 (Cdc45). Biochem. J. 409: 169–177.
Google Scholar

Yamane, K., Chen, J., Kinsella, T.J. 2003. Both DNA topoisomerase II-binding protein 1 and BRCA1 regulate the G2-M cell cycle checkpoint. Cancer Res. 63: 3049–3053.
Google Scholar

Yamane, K., Wu, X., Chen, J. 2002. A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. Mol. Cell. Biol. 22: 555–566.
Google Scholar

Yoshida, K., Inoue, I. 2004. Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F1 transcription factor. Oncogene 23: 6250–6260.
Google Scholar