Abstract
Extracellular glycoproteins of the laminin family are essential components of basement membranes involved in a number of biological processes, including tissue differentiation, wound healing, and tumorigenesis. We present the first comprehensive study of promoter methylation status of the genes encoding laminin chains in normal tissues (peripheral blood leucocytes, buccal epithelial cells, autopsy breast tissue samples) and in breast carcinoma samples. Based on the results of this study, we divide laminin genes into three categories. Genes, constitutively methylated in breast tissues include LAMA3A, LAMB2, LAMB3, and LAMC2. Genes prone to abnormal methylation in breast carcinoma include LAMA1, LAMA2, LAMA3B, LAMA4, LAMB1, and LAMC3. Genes that are rarely if ever methylated in breast carcinoma include LAMA5 and LAMC1. The constitutively methylated group includes all of the genes that encode subunits of laminin-5 (the historical name of laminin 332), the promoters of which were previously considered unmethylated in normal tissues and prone to abnormal methylation in breast cancer.
Similar content being viewed by others
References
Lyubimov A.V., Black K.L., Lyubimova Yu.Yu. 2003. Isoforms of laminin in diagnosis and prediction of progression of brain and breast tumors. Vest. RONTs im. N.N. Blokhina RAMN. 14 (3), 83–91.
Marinkovich P. 2007. Laminin 332 in squamous-cell carcinoma. Nat. Rev. Cancer. 7, 370–380.
Aumailley M., Bruckner-Tuderman L., Carter W.G., Deutzmann R., Edgar D., Ekblom P., Engel J., Engvall E., Hohenester E., Jones J.C., Kleinman H.K., Marinkovich M.P., Martin G.R., Mayer U., Meneguzzi G., Miner J.H., Miyazaki K., Patarroyo M., Paulsson M., Quaranta V., Sanes J.R., Sasaki T., Sekiguchi K., Sorokin L.M., Talts J.F., Tryggvason K., Uitto J., Virtanen I., von der Mark K., Wewer U.M., Yamada Y., Yurchenco P.D. 2005. A simplified laminin nomenclature. Matrix Biol. 24 (5), 326–332.
Lin C.Q., Bissell M.J. 1993. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 7, 737–743.
Streuli C.H., Schmidhauser C., Bailey N., Yurchenco P., Skubitz A.P.N., Roskelley C.D., Bissell M.J. 1995. Laminin mediates tissuespecific gene expression in mammary epithelia. J. Cell Biol. 129, 591–603.
Timpl R., Brown J.C. 1994. The laminins. Matrix Biol. 14 (4), 275–281.
Bergstraesser L.M., Srinivasan G., Jones J. C., Stahl S., Weitzman S.A. 1995. Expression of hemidesmosomes and component proteins is lost by invasive breast cancer cells. Am. J. Pathol. 147, 1823–1839.
Li L.C., Dahiya R. 2002. MethPrimer: designing primers for methylation PCRs. Bioinformatics. 18 (11), 1427–1431.
http://www.ncbi.nlm.nih.gov/projects/SNP.
Babenko O.V., Zemlyakova V.V., Saakyan S.V., Brovkina A.F., Strelnikov V.V., Zaletaev D.V., Nemtsova M.V. 2002. RB1 and CDKN2A functional defects resulting in retinoblastoma. Mol. Biol. (Moscow). 36 (5), 625–630.
Ryan M.C., Christiano A.M., Engvall E., Wewer U.M., Miner J.H., Sanes J.R., Burgeson R.E. 1996. The functions of laminins: lessons from in vivo studies. Matrix Biol. 15, 369–381.
Stahl S., Weitzman S., Jones J.C. 1997. The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis. J. Cell Sci. 110, 55–63.
Martin K.J., Kwan C.P., Nagasaki K., Zhang X., O’ Hare M.J., Kaelin C.M., Burgeson R.E., Pardee A.B., Sager R. 1998. Down-regulation of laminin-5 in breast carcinoma cells. Mol. Med. 4 (9), 602–613.
Nagle R.B., Hao J., Knox J.D., Dalkin B.L., Clark V., Cress A.E. 1995. Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue. Am. J. Pathol. 146, 1498–1507.
Giannelli G., Antonaci S. 2000. Biological and clinical relevance of laminin-5 in cancer. Clin. Exp. Metastasis. 18, 439–443.
Sathyanarayana U.G., Maruyama R., Padar A., Suzuki M., Bondaruk J., Sagalowsky A., Minna J.D., Frenkel E.P., Grossman H.B., Czerniak B., Gazdar A.F. 2004. Molecular detection of noninvasive and invasive bladder tumor tissues and exfoliated cells by aberrant promoter methylation of laminin-5 encoding genes. Cancer Res. 64, 1425–1430.
Sathyanarayana U.G., Padar A., Huang C.X., Suzuki M., Shigematsu H., Bekele B.N., Gazdar A.F. 2003. Aberrant promoter methylation and silencing of laminin-5encoding genes in breast carcinoma. Clin. Cancer Res. 9, 6389–6394.
Sathyanarayana U.G., Toyooka S., Padar A., Takahashi T., Brambilla E., Minna J.D., Gazdar A.F. 2003. Epigenetic inactivation of laminin-5-encoding genes in lung cancers. Clin. Cancer Res. 9, 2665–2672.
Sathyanarayana U.G., Padar A., Suzuki M., Maruyama R., Shigematsu H., Hsieh J.-H., Frenkel E., Gazdar A.F. 2003. Aberrant promoter methylation of laminin-5encoding genes in prostate cancers and its relationship to clinicopathological features. Clin. Cancer Res. 9, 6395–6400.
Zboralski D., Böckmann M., Zapatka M., Hoppe S., Schöneck A., Hahn S.A., Schmiegel W., Schwarte Waldhoff I. 2008. Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5). BMC Cancer. 8, 215.
Simonova O.A., Kuznetsova E.B., Babenko O.V., Rudenko V.V., Frank G.A., Zavalishina L.E., Kekeeva T.V., Lyubchenko L.N., Gorban’ N.A., Zaletaev D.V., Strel’nikov V.V. 2012. Methylation of genes coding for laminin-5 subunits in the norm and in breast cancer. Vest. RONTs im. N.N. Blokhina RAMN. 4, 32–38.
Kuznetsova E.B., Kekeeva T.V., Larin S.S., Zemlyakova V.V., Babenko O.V., Nemtsova M.V., Zaletaev D.V., Strelnikov V.V. 2007. Novel markers of gene methylation and expression in breast cancer. Mol. Biol. (Moscow). 41 (4), 562–570.
Lee S., Oh T., Chung H., Rha S., Kim C., Moon Y., Hoehn B. D., Jeong D., Lee S., Kim N., Park C., Yoo M., An S. 2012. Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer. Int. J. Oncol. 40 (3), 889–898.
Novaro V., Roskelley C.D., Bissell M.J. 2003. Collagen-IV and laminin-1 regulate estrogen receptor expression and function in mouse mammary epithelial cells. J. Cell Sci. 116, 2975–2986.
Spencer V.A., Costes S., Inman J.L., Xu R., Chen J., Hendzel M.J., Bissell M.J. 2011. Depletion of nuclear actin is a key mediator of quiescence in epithelial cells. J. Cell Sci. 124, 123–132.
Braakhuis B.J.M., Tabor M.P., Kummer J.A., Leemans C.R., Brakenhof R.H. 2003. A genetic explanation of Slaughter’s concept of field cancerization: Evidence and clinical implications. Cancer Res. 63, 1727–1730.
Fujita M., Khazenzon N.M., Bose S., Sekiguchi K., Sasaki T., Carter W.G., Ljubimov A.V., Black K.L., Ljubimova J.Y. 2005. Overexpression of beta1-chaincontaining laminins in capillary basement membranes of human breast cancer and its metastases. Breast Cancer Res. 7, 411–421.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © O.A. Simonova, E.B. Kuznetsova, E.V. Poddubskaya, T.V. Kekeeva, R.A. Kerimov, I.D. Trotsenko, A.S. Tanas, V.V. Rudenko, E.A. Alekseeva, D.V. Zaletayev, V.V. Strelnikov, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 4, pp. 667–677.
Rights and permissions
About this article
Cite this article
Simonova, O.A., Kuznetsova, E.B., Poddubskaya, E.V. et al. DNA methylation in the promoter regions of the laminin family genes in normal and breast carcinoma tissues. Mol Biol 49, 598–607 (2015). https://doi.org/10.1134/S0026893315040160
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893315040160