Progesterone receptor gene inactivation and CpG island hypermethylation in human leukemia cancer cells.
Previous studies showed that progesterone receptor (PR), one of the hormone receptor superfamily, was only connected with the sex-correlated cancers such as breast cancer, endometrial cancer, prostate cancer, etc. This article deals with the PR gene in leukemia. We investigated the methylation status and the expression of the two different PR isoforms, PRA and PRB, in three leukemia cancer cell lines using methylation-specific polymerase chain reaction (MSP-PCR) and reverse transcription-PCR. The correlation of PR methylation and expression together with DNA methyltransferase (DNMT1) was further studied. We found that DNMT1 is required to maintain CpG methylation and aberrant gene silencing of PR gene in human leukemia cancer cells. The activity of 5-aza-2'-deoxycytidine in demethylation and gene reactivation may be through depleting cellular DNMT1 levels. In addition, extensive methylation of PRA and PRB was also observed in leukemia samples. Our results suggest that PR CpG island aberrant hypermethylation could be one molecular and genetic alteration in leukemia.
Liu
Ze-Jun
ZJ
Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. a65424208@online.cq.cn
Zhang
Xiao-Bing
XB
Zhang
Yun
Y
Yang
Xin
X
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016022:Case-Control Studies; D018899:CpG Islands / Q000187:drug effects / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D017931:DNA Primers / Q000235:genetics; D000077209:Decitabine; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics
C411744:DMAP1 protein, human; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D012097:Repressor Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine