Premium
Promoter methylation of glutathione S‐transferase π1 and multidrug resistance gene 1 in bronchioloalveolar carcinoma and its correlation with DNA methyltransferase 1 expression
Author(s) -
Gao Peng,
Yang Xi,
Xue YuWen,
Zhang XiaoFang,
Wang Yan,
Liu WenJun,
Wu XiaoJuan
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24369
Subject(s) - gstp1 , methylation , dna methylation , methyltransferase , dnmt1 , promoter , microbiology and biotechnology , biology , cancer research , glutathione s transferase , dna methyltransferase , gene , gene expression , genetics , glutathione , genotype , enzyme , biochemistry
Abstract BACKGROUND: The presence of glutathione S‐transferase (GST) π1 (GSTP1) or multidrug resistance gene 1 (MDR1) promoter methylation in lung cancer was studied for the first time to the authors' knowledge; and, to date, the clinical significance of methylation is not clear. The objective of the current study was to determine the promoter methylation status of GSTP1 and MDR1, which encode GST‐π and P‐glycoprotein (Pgp), respectively, in patients with bronchioloalveolar carcinoma (BAC) and to investigate whether methyltransferase 1 (DNMT1)‐mediated GSTP1 or MDR1 methylation are responsible for disease progression and prognosis in patients with BAC. METHODS: Protein expression levels of DNTM1, GST‐π, and Pgp were determined by immunohistochemistry in samples from 36 patients with BAC. Promoter methylation status of the GSTP1 and MDR1 genes was determined by using methylation‐specific polymerase chain reaction analysis. RESULTS: The results demonstrated a significant correlation between the methylation of the GSTP1 or MDR1 promoters and negative expression of their respective proteins in BAC ( P < .05). A significant correlation also was demonstrated between GSTP1 methylation and recurrence‐free and overall survival of patients with BAC. DNMT1 protein expression levels were correlated with GSTP1 promoter methylation and patient prognosis ( P < .05). However, no correlation was observed between DNMT1 expression and MDR1 methylation. CONCLUSIONS: GSTP1 promoter methylation mediated by DNMT1 may promote BAC progression and could serve as a poor prognostic indicator for patients with this disease. DNMT1 protein expression also may be considered as a prognostic indicator. Methylation of the MDR1 promoter may be mediated through pathways other than DNMT1 in BAC and does not appear to be associated with disease progression or patient prognosis. Cancer 2009. © 2009 American Cancer Society.