Aberrant DNA demethylation in promoter region and aberrant expression of mRNA of PAX4 gene in hematologic malignancies.
The PAX4 gene, a member of the paired box (PAX) gene family, is thought to be involved in regulating the fate of beta-cells in the mammalian pancreas. We observed the aberrant expression of PAX4 mRNA in 10 of 15 hematologic cell lines analyzed by RT-PCR. The restoration of PAX4 gene expression after treatment with the demethylating agent 5-aza-2'-deoxycitidine, as well as bisulfite sequencing analysis, indicated that gene overexpression was caused by DNA demethylation at the promoter region. Such DNA demethylation also was observed in primary lymphoma (20 out of 45 patients) on combined bisulfite restriction assay (COBRA). Forced expression of the PAX4 gene in the HEK293 and SHSY/610 cell lines conferred positive effects on cell growth. This profile of PAX4 thus corresponds to that of a candidate oncogene in hematologic malignancies.
Li
Yinghua
Y
Clinical Research Center for Blood Diseases, National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-ku, Nagoya, Japan.
Nagai
Hirokazu
H
Ohno
Toshihito
T
Ohashi
Haruhiko
H
Murohara
Toyoaki
T
Saito
Hidehiko
H
Kinoshita
Tomohiro
T
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D019175:DNA Methylation; D000077209:Decitabine; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008199:Lymphadenitis / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine