| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Departments of Pathology*and Surgery I,Iwate Medical University School of Medicine, Morioka; and the Department of Surgery 1,Fukushima Medical University, Fukushima, Japan
Maspin, a serine protease inhibitor, was originally reported as a tumor suppressor gene in breast and prostatic cancers. We examined maspin expression and/or the allele-specific methylation status in four gastric cancer cell lines, as well as normal, metaplastic, and cancerous epithelia obtained from 50 gastric cancer patients. Three gastric cancer cell lines exhibiting maspin overexpression showed hypomethylation at either both alleles or a haploid allele. Only one cell line (GCIY) was maspin-negative but maspin expression was reactivated after treatment with a demethylating agent, 5-aza-2'-deoxycytidine. Dense and diffuse immunoreactivity for maspin was observed in 40 (80%) of 50 gastric cancers and all gastric normal epithelia (GNE) with intestinal metaplasia (IM), but not in GNE without IM. We further analyzed the allele-specific methylation status in 10 of 50 cases subjected to immunohistochemistry by the crypt isolation technique followed by a bisulfite genome sequencing method. The maspin gene promoter region of all GNE without IM was hypermethylated on both alleles whereas those with IM frequently represented the haploid type of hypomethylation status. In six of seven gastric cancers in which crypt isolation was possible, demethylation frequently occurred and extended to both alleles. Maspin mRNA was amplified from GNE with IM and cancerous crypts but not from GNE without IM. These results suggest that demethylation at the maspin gene promoter disrupts the cell-type-specific gene repression in both GNE and gastric cancer.
This article has been cited by other articles:
 |
|
 |
|
  Y. Kanai and S. Hirohashi Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state Carcinogenesis, December 1, 2007; 28(12): 2434 - 2442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Woenckhaus, L. Bubendorf, P. Dalquen, J. Foerster, H. Blaszyk, M. Mirlacher, M. Soler, W. Dietmaier, G. Sauter, A. Hartmann, et al. Nuclear and cytoplasmic Maspin expression in primary non-small cell lung cancer J. Clin. Pathol., May 1, 2007; 60(5): 483 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J J L Wong, N J Hawkins, and R L Ward Colorectal cancer: a model for epigenetic tumorigenesis Gut, January 1, 2007; 56(1): 140 - 148. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Khalkhali-Ellis Maspin: The New Frontier Clin. Cancer Res., December 15, 2006; 12(24): 7279 - 7283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Maesawa, S Ogasawara, A Yashima-Abo, T Kimura, K Kotani, S Masuda, Y Nagata, T Iwaya, K Suzuki, T Oyake, et al. Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis. J. Clin. Pathol., March 1, 2006; 59(3): 328 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kim, J. Han, J. Kim, and C. Park Maspin Expression Is Transactivated by p63 and Is Critical for the Modulation of Lung Cancer Progression Cancer Res., October 1, 2004; 64(19): 6900 - 6905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. E. Domann and B. W. Futscher Flipping the Epigenetic Switch Am. J. Pathol., June 1, 2004; 164(6): 1883 - 1886. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
