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The expression of metastasis suppressor MIM/MTSS1 is regulated by DNA methylation
Author(s) -
Utikal Jochen,
Gratchev Alexei,
MullerMolinet Isabelle,
Oerther Sandra,
Kzhyshkowska Julia,
Arens Norbert,
Grobholz Rainer,
Kannookadan Sheila,
Goerdt Sergij
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22106
Subject(s) - dna methylation , methylation , biology , cpg site , promoter , microbiology and biotechnology , bisulfite sequencing , cell culture , cell growth , cancer research , dna , gene expression , gene , genetics
Abstract MIM/MTSS1 was initially described as a gene missing in invasive bladder cancer cell lines. Functional analysis revealed that MIM is an actin binding protein involved in the regulation of actin cytoskeleton dynamics. MIM was shown to be sonic hedgehog (Shh) signaling dependent and synergizes with the effects of Gli transcription factors. Overexpression of MIM in cell lines leads to the inhibition of cell proliferation. In this study, we showed that the inhibition of cell growth by MIM is anchorage independent. We identified and cloned the promoter region of MIM and located the main promoter activity to 276 bp of 5′ flanking sequence sited within a CpG island. Analysis of DNA methylation using bisulphite sequencing revealed that MIM promoter is methylated in its 5′ region in cells and tissue samples with reduced endogenous MIM expression. Using luciferase reporter assay, we demonstrated that nonmethylated MIM promoter has a similar activity in cell lines with different endogenous MIM expression. Inhibition of DNA methylation by 5‐Aza‐2′‐deoxycytidine led to upregulation of MIM expression in a low expressing cell line. In conclusion, we clearly demonstrate here that the expression of metastasis suppressor MIM is regulated by DNA methylation of a CpG island within its promoter region. © 2006 Wiley‐Liss, Inc.