Hypermethylation and histone deacetylation lead to silencing of the maspin gene in human breast cancer.
Maspin is a member of the serine protease inhibitor family with tumor suppressing activity in breast cancer. Maspin expression was found in normal breast epithelial cells, but was frequently decreased in breast cancer cells and lost in metastatic cells. In this study, we examined the regulatory mechanism of maspin expression and described the re-activation of maspin expression in a series of maspin-negative breast cancer cell lines. All of the 6 maspin-negative breast cancer cells showed induction of maspin promoter activity in a promoter reporter assay. In addition, the treatment of 5-aza-2(') deoxycytidine, trichostatin A or a combination of both led to the re-expression of maspin in a series of maspin-negative breast cancer cell lines. These findings indicate that DNA methylation and/or histone deacetylation are/is partially responsible for the silencing of maspin gene expression in breast cancer cells. The re-expression of maspin by pharmacological intervention potentially offers a promising new target as a therapeutic option in breast cancer.
Maass
Nicolai
N
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany.
Biallek
Marco
M
Rösel
Frank
F
Schem
Christian
C
Ohike
Nobuyuki
N
Zhang
Ming
M
Jonat
Walter
W
Nagasaki
Koichi
K
D000107:Acetylation; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011506:Proteins / Q000235:genetics*; D015843:Serpins / Q000235:genetics*; D014407:Tumor Cells, Cultured
D006657:Histones; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins