MRTF-A transactivates COMT gene and decreases the anti-tumor effects of tamoxifen


Myocardin-related transcription factors A (MRTF-A) is a myocardin-related transcription factor that have been found strongly activated CarG box–containing genes through its direct binding to serum response factor (SRF). In the present study, the MRTF-A ex-pression vector was constructed. The MTT assay showed that transfection of MRTF-A could significantly decrease the anti-tumor effect of tamoxifen on MCF-7 breast cancer cells. The bioinformatics analysis found that the CarG element existed in the pro-moter region of COMT gene of many familiar verte-brates, including of human, rhesus macaque, chimpanzee, etc. The results of RT-PCR assay further showed that MRTF-A could enhance the transcrip-tion level of COMT. These results are the first to indicate that COMT might be a target gene which could be regulated by MRTF-A/SRF, and such transactivation event might be involved in the process of tamoxifen resistance.

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Liu, Z. , Luo, X. , Guo, S. , Wang, J. , Zhang, X. , Wang, N. , Jiang, Y. and Zhang, T. (2009) MRTF-A transactivates COMT gene and decreases the anti-tumor effects of tamoxifen. Journal of Biomedical Science and Engineering, 2, 559-563. doi: 10.4236/jbise.2009.27081.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Deroo, B. J. and Korach, K. S., (2006) Estrogen receptors and human disease, J. Clin. Invest. Ann. Arbor., 116, 561–570.
[2] Ring, A., and Dowsett, M., (2004) Mechanisms of tamoxifen resistance, Endocr-relat cancer, Bristol., 11, 643–658.
[3] Wang, D. Z., Li, S., Hockemeyer, D., Sutherland, L., Wang, Z., Schratt, G., et al, (2002) Potentiation of serum response factor activity by a family of myocardin-related transcription factors, Proc. Natl. Acad. Sci., USA, Washington, 99, 14855–14860.
[4] Teg Pipes, G. C., Creemers, E. E., and Olson, E. N., (2006) The myocardin family of transcriptional coactivators: Versatile regulators of cell growth, migration, and myogenesis, Gene dev, Cold Spring Harbor, 20, 1545– 1556.
[5] Sun, Y., Boyd, K., Xu, W., Ma, J., Jackson, C. W., Fu, A., et al, (2006) Acute myeloid leukemia-associated mkl1 (mrtf-a) is a key regulator of mammary gland function, Mol. Cell Biol., Washington, 26, 5809–5826.
[6] Li, S., Chang, S., Qi, X., Richardson, J. A., and Olson, E. N., (2006) Requirement of a myocardin-ralated transcription factor for development of mammary myoepithelial cells, Mol. Cell Biol., Washington, 26, 5797–5808.
[7] Sun, Q., Chen, G., Streb, J. W., Long, X., Yang, Y., Stoeckert, C. J., et al, (2006) Defining the mammalian CarGome, Genome. Res., Cold Spring Harbor, 16, 197– 207.
[8] Jordan, V. C., (2003) Is tamoxifen the rosetta stone for breast cancer, J. Natl. Cancer. Inst. Bethesda, 95, 338– 340.
[9] Hilsenbeck, S. G., Friedrichs, W. E., Schiff, R., O’Connell, P., Hansen, R. K., Osborne, C. K., et al, (1999) Statistical analysis of array expression data as applied to the problem of tamoxifen resistance, J. Natl. Cancer. Inst. Bethesda, 91, 453–459.
[10] Mannisto, P. T. and Kaakkola, S., (2008) Catechol-O- methyl-transferase (COMT): Biochemistry, molecular biology, phar-macology, and clinical efficacy of the new selective COMT inhibitors, Pharmacol. rev. Bethesda, 51, 593–628.
[11] Singh, M. N., Stringfellow, H. E., Walsh, M. J., Ashton, K. M., Paraskevaidis, E., Abdo, K. R., et al, (2008) Quantifiable mRNA transcripts for tamoxifen-metabolising enzymes in hu-man endometrium, Toxicology, Limerick, 249, 85–90.
[12] Dehal, S. S. and Kupfer, D., (1995) Evidence that the catechol 3, 4-dihydroxytamosifen is a proximate intermediate to the reactive species binding covalently to proteins, Cancer Res. Baltimore, 56, 1283–1290.
[13] Cen, B., Selvaraj, A., Burgess, R. C., Hitzler, J. K., Ma, Z., Morris, S. W., et al, (2003) Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes, Mol Cell Biol., Washington, 23, 6597– 6606.
[14] Dubey, R. K., Gillespie, D. G., Zacharia, L. C., Barchiesi, F., Imthurn, B., and Jackson, E. K., (2003) CYP450- and COMT-derived estradiol metabolites inhibit activity of human coronary artery SMCs, Hypertension, Dallas, 41, 807–813.
[15] Dubey, R. K., Tofovic, S. P., and Jackson, E. K., (2004) Car-diovascular pharmacology of estradiol metabolites, J. Pharma-col. Exp. Ther., Bethesda, 308, 403–409.
[16] Wentz, M. J., Jamaluddin, M., Garfield, R. E., Al-Hendy, A., (2006) Regulation of catechol-O-methyltransferase expression in human myometrial cells, Obstet. Gynecol., Hagerstown, 108, 1439–1447.

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