Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa
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Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa. / Gao, Shan; Nielsen, Boye Schnack; Krogdahl, Annelise; Sørensen, Jens Ahm; Tagesen, Jan; Dabelsteen, Sally; Dabelsteen, Erik; Andreasen, Peter.
I: Genes, Chromosomes & Cancer, Bind 49, Nr. 6, 01.06.2010, s. 526-38.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa
AU - Gao, Shan
AU - Nielsen, Boye Schnack
AU - Krogdahl, Annelise
AU - Sørensen, Jens Ahm
AU - Tagesen, Jan
AU - Dabelsteen, Sally
AU - Dabelsteen, Erik
AU - Andreasen, Peter
N1 - (c) 2010 Wiley-Liss, Inc.
PY - 2010/6/1
Y1 - 2010/6/1
N2 - A high level of plasminogen activator inhibitor-1 (PAI-1 or SERPINE1) in tumor extracts is a marker of a poor prognosis in human cancers, including oral carcinomas. However, the mechanisms responsible for the upregulation of PAI-1 in cancers remain unclear. Investigating specific PAI-1 expressing cells in oral carcinomas by immunohistochemistry, we found that PAI-1 was expressed in 18 of the 20 patients, mainly by cancer cells. Two showed PAI-1 positive stromal cells surrounding the tumor areas and five showed PAI-1 positive cells in tumor-adjacent normal epithelium. By real-time RT-PCR analysis, 17 of 20 patients with oral carcinoma were found to have between 2.5- and 50-fold increased tumor PAI-1 mRNA level, as compared with the matched tumor-adjacent normal tissues. The PAI-1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor-adjacent normal tissues, but the level in epithelium was 5- to 10-fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor-adjacent normal tissue had a significant level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor-adjacent normal tissue already contains transformation-associated epigenetic changes. However, there was no general inverse correlation between PAI-1 mRNA levels and SERPINE1 gene methylation in all tissues, showing that CpG methylation is not the main determinant of the PAI-1 expression level in oral tissue.
AB - A high level of plasminogen activator inhibitor-1 (PAI-1 or SERPINE1) in tumor extracts is a marker of a poor prognosis in human cancers, including oral carcinomas. However, the mechanisms responsible for the upregulation of PAI-1 in cancers remain unclear. Investigating specific PAI-1 expressing cells in oral carcinomas by immunohistochemistry, we found that PAI-1 was expressed in 18 of the 20 patients, mainly by cancer cells. Two showed PAI-1 positive stromal cells surrounding the tumor areas and five showed PAI-1 positive cells in tumor-adjacent normal epithelium. By real-time RT-PCR analysis, 17 of 20 patients with oral carcinoma were found to have between 2.5- and 50-fold increased tumor PAI-1 mRNA level, as compared with the matched tumor-adjacent normal tissues. The PAI-1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor-adjacent normal tissues, but the level in epithelium was 5- to 10-fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor-adjacent normal tissue had a significant level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor-adjacent normal tissue already contains transformation-associated epigenetic changes. However, there was no general inverse correlation between PAI-1 mRNA levels and SERPINE1 gene methylation in all tissues, showing that CpG methylation is not the main determinant of the PAI-1 expression level in oral tissue.
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Squamous Cell
KW - Case-Control Studies
KW - Chi-Square Distribution
KW - DNA Methylation
KW - Epigenesis, Genetic
KW - Female
KW - Gene Expression Profiling
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Middle Aged
KW - Mouth Mucosa
KW - Mouth Neoplasms
KW - Plasminogen Activator Inhibitor 1
KW - Polymorphism, Genetic
KW - Promoter Regions, Genetic
KW - Reverse Transcriptase Polymerase Chain Reaction
U2 - 10.1002/gcc.20762
DO - 10.1002/gcc.20762
M3 - Journal article
C2 - 20222049
VL - 49
SP - 526
EP - 538
JO - Genes, Chromosomes & Cancer
JF - Genes, Chromosomes & Cancer
SN - 1045-2257
IS - 6
ER -
ID: 33676884