Skip to main content
Top
Published in: Pathology & Oncology Research 3/2011

01-09-2011 | Research

The Influence of Methylated Septin 9 Gene on RNA and Protein Level in Colorectal Cancer

Authors: Kinga Tóth, Orsolya Galamb, Sándor Spisák, Barnabás Wichmann, Ferenc Sipos, Gábor Valcz, Katalin Leiszter, Béla Molnár, Zsolt Tulassay

Published in: Pathology & Oncology Research | Issue 3/2011

Login to get access

Abstract

Colorectal cancer is one of the leading death causes in the world. Specificity and sensitivity of the present screening methods are unsuitable and their compliance is too low. Nowadays the most effective method is the colonoscopy, because it gives not only macroscopic diagnosis but therapeutic possibility as well, however the compliance of the patients is very low. Hence development of new diagnostic methods is needed. Altered expression of septin 9 was found in several tumor types including colorectal cancer. The aim of this study was to detect the methylation related mRNA and protein expression changes of septin 9 in colorectal adenoma-dysplasia-carcinoma sequence and to analyze its reversibility by demethylation treatment. Septin 9 protein expression showed significant difference between normal and colorectal cancer (CRC) samples (p < 0,001). According to biopsy microarray results, septin 9 mRNA expression decreased in the progression of colon neoplastic disease (p < 0,001). In laser microdissected epithelial cells, septin 9 significantly underexpressed in CRC compared to healthy controls (p < 0,001). The expression of septin9_v1 region was higher in the healthy samples, while septin9_v2, v4, v4*, v5 overexpression were detected in cancer epithelial cells compared to normal. The septin 9 mRNA and protein levels of HT29 cells increased after demethylation treatment. The increasing methylation of septin 9 gene during colorectal adenoma-dysplasia-carcinoma sequence progression is reflected in the decreasing mRNA and protein expression, especially in the epithelium. These changes can be reversed by demethylation agents converting this screening marker gene into therapeutic target.
Literature
1.
2.
3.
go back to reference Ebert MP, Model F, Mooney S et al (2006) Aristaless-like homeobox-4 gene methylation is a potential marker for colorectal adenocarcinomas. Gastroenterology 131:1418–1430PubMedCrossRef Ebert MP, Model F, Mooney S et al (2006) Aristaless-like homeobox-4 gene methylation is a potential marker for colorectal adenocarcinomas. Gastroenterology 131:1418–1430PubMedCrossRef
4.
go back to reference Lofton-Day C, Model F, Devos T et al (2008) DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem 54:414–423PubMedCrossRef Lofton-Day C, Model F, Devos T et al (2008) DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem 54:414–423PubMedCrossRef
5.
go back to reference Grützmann R, Molnar B, Pilarsky C et al (2008) Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS ONE 3:e3759PubMedCrossRef Grützmann R, Molnar B, Pilarsky C et al (2008) Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PLoS ONE 3:e3759PubMedCrossRef
6.
go back to reference Devos T, Tetzner R, Model F et al (2009) Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 55:1337–1346PubMedCrossRef Devos T, Tetzner R, Model F et al (2009) Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 55:1337–1346PubMedCrossRef
7.
go back to reference Scott M, Hyland PL, McGregor G et al (2005) Multimodality expression profiling shows SEPT9 to be overexpressed in a wide range of human tumours. Oncogene 24:4588–4700CrossRef Scott M, Hyland PL, McGregor G et al (2005) Multimodality expression profiling shows SEPT9 to be overexpressed in a wide range of human tumours. Oncogene 24:4588–4700CrossRef
8.
go back to reference Galamb O, Györffy B, Sipos F (2008) Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers 25:1–16PubMed Galamb O, Györffy B, Sipos F (2008) Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers 25:1–16PubMed
9.
10.
go back to reference Russell SE, McIlhatton MA, Burrows JF (2000) Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors. Cancer Res 60:4729–4734PubMed Russell SE, McIlhatton MA, Burrows JF (2000) Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors. Cancer Res 60:4729–4734PubMed
11.
go back to reference Kalikin LM, Sims HL, Petty EM (2000) Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors. Genomics 63:165–172PubMedCrossRef Kalikin LM, Sims HL, Petty EM (2000) Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors. Genomics 63:165–172PubMedCrossRef
12.
go back to reference Burrows JF, Chanduloy S, McIlhatton MA et al (2003) Altered expression of the septin gene, SEPT9, in ovarian neoplasia. J Pathol 201:581–588PubMedCrossRef Burrows JF, Chanduloy S, McIlhatton MA et al (2003) Altered expression of the septin gene, SEPT9, in ovarian neoplasia. J Pathol 201:581–588PubMedCrossRef
13.
go back to reference Montagna C, Lyu MS, Hunter K et al (2003) The Septin 9 (MSF) gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines. Cancer Res 63:2179–2187PubMed Montagna C, Lyu MS, Hunter K et al (2003) The Septin 9 (MSF) gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines. Cancer Res 63:2179–2187PubMed
14.
go back to reference Tatsumi K, Taki T, Taniwaki M et al (2001) The CDCREL1 gene fused to MLL in de novo acute myeloid leukemia with t(11;22)(q23;q11.2) and its frequent expression in myeloid leukemia cell lines. Genes Chromosom Cancer 30:230–235PubMedCrossRef Tatsumi K, Taki T, Taniwaki M et al (2001) The CDCREL1 gene fused to MLL in de novo acute myeloid leukemia with t(11;22)(q23;q11.2) and its frequent expression in myeloid leukemia cell lines. Genes Chromosom Cancer 30:230–235PubMedCrossRef
15.
go back to reference Kim HJ, Ki CS, Park Q et al (2003) MLL/SEPTIN6 chimeric transcript from invins(X;11)(q24;q23q13) in acute monocytic leukemia: report of a case and review of the literature. Genes Chromosom Cancer 38:8–12PubMedCrossRef Kim HJ, Ki CS, Park Q et al (2003) MLL/SEPTIN6 chimeric transcript from invins(X;11)(q24;q23q13) in acute monocytic leukemia: report of a case and review of the literature. Genes Chromosom Cancer 38:8–12PubMedCrossRef
16.
go back to reference Kojima K, Sakai I, Hasegawa A et al (2004) FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23). Leukemia 18:998–1005PubMedCrossRef Kojima K, Sakai I, Hasegawa A et al (2004) FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23). Leukemia 18:998–1005PubMedCrossRef
17.
go back to reference Tanaka M, Tanaka T, Matsuzaki S et al (2003) Rapid and quantitative detection of human septin family Bradeion as a practical diagnostic method of colorectal and urologic cancers. Med Sci Monit 9:61–68 Tanaka M, Tanaka T, Matsuzaki S et al (2003) Rapid and quantitative detection of human septin family Bradeion as a practical diagnostic method of colorectal and urologic cancers. Med Sci Monit 9:61–68
18.
go back to reference Kim DS, Hubbard SL, Peraud A et al (2004) Analysis of mammalian septin expression in human malignant brain tumors. Neoplasia 6:168–178PubMedCrossRef Kim DS, Hubbard SL, Peraud A et al (2004) Analysis of mammalian septin expression in human malignant brain tumors. Neoplasia 6:168–178PubMedCrossRef
19.
go back to reference Model F, Osborn N, Ahlquist D et al (2007) Identification and validation of colorectal neoplasia-specific methylation markers for accurate classification of disease. Mol Cancer Res 5:153–163PubMedCrossRef Model F, Osborn N, Ahlquist D et al (2007) Identification and validation of colorectal neoplasia-specific methylation markers for accurate classification of disease. Mol Cancer Res 5:153–163PubMedCrossRef
20.
go back to reference Tóth K, Galamb O, Spisák S et al (2009) Free circulating DNA based colorectal cancer screening from peripheral blood: the possibility of the methylated septin 9 gene marker. Orv Hetil 150:969–977PubMedCrossRef Tóth K, Galamb O, Spisák S et al (2009) Free circulating DNA based colorectal cancer screening from peripheral blood: the possibility of the methylated septin 9 gene marker. Orv Hetil 150:969–977PubMedCrossRef
21.
go back to reference Scott M, McCluggage WG, Hillan KJ et al (2006) Altered patterns of transcription of the septin 9 gene, SEPT9, in ovarian tumorigenesis. Int J Cancer 118:1325–1329PubMedCrossRef Scott M, McCluggage WG, Hillan KJ et al (2006) Altered patterns of transcription of the septin 9 gene, SEPT9, in ovarian tumorigenesis. Int J Cancer 118:1325–1329PubMedCrossRef
22.
go back to reference Montagna C, Lyu MS, Hunter K (2003) The Septin 9 (MSF) gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines. Cancer Res 63:2179–2187PubMed Montagna C, Lyu MS, Hunter K (2003) The Septin 9 (MSF) gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines. Cancer Res 63:2179–2187PubMed
23.
go back to reference Gonzalez ME, Peterson EA, Privette LM (2007) High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. Cancer Res 67:8554–8564PubMedCrossRef Gonzalez ME, Peterson EA, Privette LM (2007) High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. Cancer Res 67:8554–8564PubMedCrossRef
24.
go back to reference Liu ZJ, Wang G, Cai Y (2009) Androgen receptor CpG island methylation status in human leukemia cancer cells. Cancer Investig 27:156–162CrossRef Liu ZJ, Wang G, Cai Y (2009) Androgen receptor CpG island methylation status in human leukemia cancer cells. Cancer Investig 27:156–162CrossRef
25.
go back to reference Yap OW, Bhat G, Liu L et al (2009) Epigenetic modifications of the Estrogen receptor beta gene in epithelial ovarian cancer cells. Anticancer Res 29:139–144PubMed Yap OW, Bhat G, Liu L et al (2009) Epigenetic modifications of the Estrogen receptor beta gene in epithelial ovarian cancer cells. Anticancer Res 29:139–144PubMed
26.
go back to reference Deng G, Kakar S, Okudiara K et al (2009) Unique methylation pattern of oncostatin m receptor gene in cancers of colorectum and other digestive organs. Clin Cancer Res 15:1519–1526PubMedCrossRef Deng G, Kakar S, Okudiara K et al (2009) Unique methylation pattern of oncostatin m receptor gene in cancers of colorectum and other digestive organs. Clin Cancer Res 15:1519–1526PubMedCrossRef
Metadata
Title
The Influence of Methylated Septin 9 Gene on RNA and Protein Level in Colorectal Cancer
Authors
Kinga Tóth
Orsolya Galamb
Sándor Spisák
Barnabás Wichmann
Ferenc Sipos
Gábor Valcz
Katalin Leiszter
Béla Molnár
Zsolt Tulassay
Publication date
01-09-2011
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 3/2011
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-010-9338-7

Other articles of this Issue 3/2011

Pathology & Oncology Research 3/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine