The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer.
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.
Semmelweis University, 2nd Department of Internal Medicine, Budapest, Hungary. drtothkinga@yahoo.com
Kinga
K
Tóth
Orsolya
O
Galamb
Sándor
S
Spisák
Barnabás
B
Wichmann
Ferenc
F
Sipos
Gábor
G
Valcz
Katalin
K
Leiszter
Béla
B
Molnár
Zsolt
Z
Tulassay
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D061346:Laser Capture Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058112:Septins / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C474315:SEPTIN9 protein, human; D058112:Septins
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