Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2.
We analyzed gene expression of MBD1, MBD2, MBD3, MBD4, and MeCP2 and protein expression of MBD1, MBD2, and MeCP2 in prostate cancer cell lines, benign prostate epithelium (BPH-1) cell line, 49 BPH tissues, and 46 prostate cancer tissues. The results of this study demonstrate that MBD2 gene is expressed in all samples and MeCP2 gene is expressed in all cancer cell lines but not in BPH-1 cell line. However, there was no protein expression for MBD2 and MeCP2 in cancer cell lines and cancer tissues. For CXXC sequence containing MBD1, both protein and mRNA were expressed in cancer cell lines, cancer tissues, BPH-1 cell line, and BPH tissues. We observed that, in BPH tissues and low-grade cancer tissues, MBD1 protein expression was very high and gradually decreased with increase of cancer grade. Treatment of cancer cell lines with proteasome inhibitor (MG-132) did not restore expression of MBD2 and MeCP2 proteins. When prostate cancer cell lines were treated with hypomethylating agent, 5-aza-2(')-deoxycytidine (DNMT inhibitor), HDAC1 and HDAC2 expression was decreased. This is the first report demonstrating that CXXC sequence containing MBD1 is overexpressed and can be the major factor of hypermethylated chromatin segments through HDAC1/2 translocation and histone deacetylation in human prostate cancer.
Patra
Samir K
SK
Department of Urology, Urology Research Center (112F), University of California at San Francisco and Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
Patra
Aditi
A
Zhao
Hong
H
Carroll
Peter
P
Dahiya
Rajvir
R
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000378:metabolism; D001374:Azacitidine / Q000378:metabolism; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D007976:Leupeptins; C066141:MBD1 protein, human; C115368:MBD2 protein; C489325:MBD2 protein, human; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases; D001374:Azacitidine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde