Abstract
The tissue kallikrein gene family consists of 15 genes tandemly arranged on human chromosome 19q13.4. Most kallikrein genes are characterized by aberrant expression patterns in various human cancers, a feature that makes them ideal cancer biomarkers. In the present study, we investigated the effect of the epigenetic drug compound 5-aza-2′-deoxycytidine on the expression of downregulated kallikrein genes in prostate, breast, and ovarian cancer cell lines. Reactivation of multiple kallikrein genes was observed, although some of these genes do not contain CpG islands in their genomic sequence. Epigenetic regulation provides a new mechanism for the pharmacological modulation of kallikreins in human cancers with putative therapeutic implications.
References
Borgono, C.A. and Diamandis, E.P. (2004). The emerging roles of human tissue kallikreins in cancer. Nat. Rev. Cancer4, 876–890.10.1038/nrc1474Search in Google Scholar
Christophi, G.P., Isackson, P.J., Blaber, S., Blaber, M., Rodriguez, M., and Scarisbrick, I.A. (2004). Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease. J. Neurochem.91, 1439–1449.10.1111/j.1471-4159.2004.02826.xSearch in Google Scholar
Evans, B.A., Yun, Z.X., Close, J.A., Tregear, G.W., Kitamura, N., Nakanishi, S., Callen, D.F., Baker, E., Hyland, V.J., Sutherland, G.R., and Richards, R.I. (1988). Structure and chromosomal localization of the human renal kallikrein gene. Biochemistry27, 3124–3129.10.1021/bi00409a003Search in Google Scholar
Gan, L., Lee, I., Smith, R., Argonza-Barrett, R., Lei, H., McCuaig, J., Moss, P., Paeper, B., and Wang, K. (2000). Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene257, 119–130.10.1016/S0378-1119(00)00382-6Search in Google Scholar
Harvey, T.J., Hooper, J.D., Myers, S.A., Stephenson, S.A., Ashworth, L.K., and Clements, J.A. (2000). Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J. Biol. Chem.275, 37397–37406.10.1074/jbc.M004525200Search in Google Scholar
Johnstone, R.W. (2002). Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat. Rev. Drug Discov.1, 287–299.10.1038/nrd772Search in Google Scholar
Jones, P.A. and Baylin, S.B. (2002). The fundamental role of epigenetic events in cancer. Nat. Rev. Cancer3, 415–428.10.1038/nrg816Search in Google Scholar
Lazzaro, G., Agadir, A., Qing, W., Poria, M., Mehta, R.R., Moriarty, R.M., Das Gupta, T.K., Zhang, X.K., and Mehta, R.G. (2000). Induction of differentiation by 1α-hydroxyvitamin D5 in T47D human breast cancer cells and its interaction with vitamin D receptors. Eur. J. Cancer36, 780–786.10.1016/S0959-8049(00)00016-2Search in Google Scholar
Li, B., Goyal, J., Dhar, S., Dimri, G., Evron, E., Sukumar, S., Wazer, E.D., and Band, V. (2001). CpG methylation as a basis for breast tumor-specific loss of NES1/kallikrein 10 expression. Cancer Res.61, 8014–8021.Search in Google Scholar
Lin, R., Nagai, Y., Sladek, R., Bastien, Y., Ho, J., Petrecca, K., Sotiropoulou, G., Diamandis, E.P., Hudson, T.J., and White, J.H. (2002). Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol. Endocrinol.16, 1243–1256.10.1210/mend.16.6.0874Search in Google Scholar PubMed
Lyko, F. and Brown, R. (2005). DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl. Cancer Inst.97, 1498–1506.10.1093/jnci/dji311Search in Google Scholar PubMed
Nakamura, T., Mitsui, S., Okui, A., Kominami, K., Nomoto, T., Ukimura, O., Kawauchi, A., Miki, T., and Yamaguchi, N. (2001). Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines. Prostate49, 72–78.10.1002/pros.1119Search in Google Scholar
Palmer, H.G., Sanchez-Carbayo, M., Ordonez-Moran, P., Larriba, M.J., Cordon-Cardo, C., and Munoz, A. (2003). Genetic signatures of differentiation induced by 1α,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res.63, 7799–7806.Search in Google Scholar
Pampalakis, G., Kurlender, L., Diamandis, E.P., and Sotiropoulou, G. (2004). Cloning and characterization of novel isoforms of the human kallikrein 6 gene. Biochem. Biophys. Res. Commun.320, 54–61.10.1016/j.bbrc.2004.04.205Search in Google Scholar
Papsidero, L.D., Wang, M.C., Valenzuela, L.A., Murphy, G.P., and Chu, T.M. (1980). A prostate antigen in sera of prostatic cancer patients. Cancer Res.40, 2428–2432.Search in Google Scholar
Qin, H., Kemp, J., Yip, M., Lam-Po-Tang, P.R.L., and Morris, B.J. (1991). Localization of human glandular kallikrein-1 gene to chromosome 19q13.3-13.4 by in situ hybridization. Hum. Hered.41, 222–226.Search in Google Scholar
Richards, R.I., Holman, K., Shen, Y., Kozman, H., Harley, H., Brook, D., Shaw, D. (1991). Human glandular kallikrein genes: genetic and physical mapping of the KLK1 locus using a highly polymorphic microsatellite PCR marker. Genomics11, 77–82.10.1016/0888-7543(91)90103-LSearch in Google Scholar
Riegman, P.H.J., Vlietstra, R.J., Klaassen, P., Van der Korput, J.A.G.M., Guerts van Kessel, A., Romijn, J.C., and Trapman, J. (1989). The prostate-specific antigen gene and the human glandular kallikrein-1 gene are tandemly located on chromosome 19. FEBS Lett.247, 123–126.10.1016/0014-5793(89)81253-0Search in Google Scholar
Riegman, P.H.J., Vlietstra, R.J., Suurmeijer, L., Cleutjens, C.B.J.M., and Trapman, J. (1992). Characterization of the human kallikrein locus. Genomics14, 6–11.10.1016/S0888-7543(05)80275-7Search in Google Scholar
Rittenhouse, H.G., Finlay, J.A., Mikolajczyk, S.D., and Partin, A.W. (1988). Human kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit. Rev. Clin. Lab. Sci.35, 275–368.Search in Google Scholar
Roman-Gomez, J., Jimenez-Velasco, A., Agirre, X., Castillejo, J.A., Barrios, M., Andreu, E.J., Prosper, F., Heiniger, A., and Torres, A. (2004). The normal epithelial cell-specific 1 (NES1) gene, a candidate tumor suppressor gene on chromosome 19q13.3-4, is downregulated by hypermethylation in acute lymphoblastic leukemia. Leukemia18, 362–365.Search in Google Scholar
Sidiropoulos, M., Pampalakis, G., Sotiropoulou, G., Katsaros, D., Diamandis, E.P. (2005). Downregulation of human kallikrein 10 (KLK10/NES1) gene by CpG island hypermethylation in breast, ovarian and prostate cancers. Tumor Biol.26, 324–336.10.1159/000089290Search in Google Scholar PubMed
Wang, M.C., Valenzuela, L.A., Murphy, G.P., and Chu, T.M. (1977). Tissue specific and tumor specific antigens in human prostate. Fed. Proc.36, 1254.Search in Google Scholar
Wang, M.C., Valenzuela, L.A., Murphy, G.P., and Chu, T.M. (1979). Purification of a human prostate-specific antigen. Invest. Urol.17, 159–163.Search in Google Scholar
Wang, M.C., Papsidero, L.D., Kuriyama, M., Valenzuela, L.A., Murphy, G.P., and Chu, T.M. (1981). Prostate antigen: a new potential marker for prostatic cancer. Prostate21, 89–96.10.1002/pros.2990020109Search in Google Scholar PubMed
Xi, Z., Kaern, J., Davidson, B., Klokk, T.I., Risberg, B., Trope, C., and Saatcioglu, F. (2004). Kallikrein 4 is associated with paclitaxel resistance in ovarian cancer. Gynecol. Oncol.94, 80–85.10.1016/j.ygyno.2004.03.044Search in Google Scholar PubMed
Yousef, G.M. and Diamandis, E.P. (2001). The new human tissue kallikrein gene family: structure, function and association to disease. Endocr. Rev.22, 184–204.Search in Google Scholar
Yousef, G.M., Chang, A., Scorilas, A., and Diamandis, E.P. (2000). Genomic organization of the human kallikrein gene family on chromosome 19q13.3–q13.4. Biochem. Biophys. Res. Commun.16, 125–133.10.1006/bbrc.2000.3448Search in Google Scholar PubMed
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