Expression profile of significant immortalization genes in colon cancer

Abstract

Abstract.Cancer is a disease of genomic instability, a multistep process involving numerous mutations and chromosomal aberrations. Telomeres are highly specialized structures at the ends of chromosomes and function to stabilize and protect the ends of linear chromosomes, therefore determining cellular immortalization. Homeostasis of telomere length is a multifactor-dependent process. Since cellular immortalization is an early and essential step towards cancer, the aim of the present study was to determine immortalization genes that are significant in colon cancer and assess their usefulness in the early diagnosis of this tumor. Expression profiles of 119 transcripts known to be involved in cellular immortalization were assessed with oligonucleotide microarrays in 13 probes of colon adenocarcinoma (low and high clinical stages) and 9 probes of controls (normal colon tissue) and were compared among these groups with the use of the Significant Analysis Microarray (SAM) software and independently verified with the effect size parameter. Eighteen genes with significantly differential expression between high clinical stage colon cancer and the control group, and 21 with differential expression between low clinical stage colon cancer and the control group were identified. Nine genes showing altered expression in both low and high clinical stage colon cancer: ACD (TPP1), DKC1 and ERCC1, MYC, MAX, NBN, NOLA2, PRKDC and HSP82 should, in particular, be the subjects of further studies including QRT-PCR methods.

Dyskerin Overexpression in Human Hepatocellular Carcinoma Is Associated with Advanced Clinical Stage and Poor Patient Prognosis

“…Our results established that the protein and mRNA expression of dyskerin was significantly higher in HCC tissues than in non-malignant liver tissues. While this gene has previously been reported to be a tumor suppressor gene [5], [24], the quantitative analysis of dyskerin expression performed on a series of human cancers showed a dramatically increased dyskerin expression in certain types of tumors, including prostate cancer [17], colon cancer [18] and colorectal cancer [19]. Our IHC results demonstrated that the high expression of dyskerin was significantly correlated with advanced clinical stages (III and IV) of HCC.…”

“…The overexpression of dyskerin has been reported previously in several cancers, including neuroblastoma [12], lymphoma [13], melanoma [14], breast cancer [15], [16], prostate cancer [17], colorectal cancer [18], [19], and ovarian carcinoma [20]. A previous study also showed that dyskerin is required for tumor cell growth through mechanisms that are independent of its role in telomerase and only partially related to its function in precursor rRNA processing [21].…”

Downregulation of telomerase maintenance-related ACD expression in patients undergoing immunosuppresive therapy following kidney transplantation

“…In stage 1, differential factors were identified among 70 genes (123 transcripts) involved in telomere maintenance. The genes were selected in accordance with the method described in detail by Witkowska et al (21). Among the analyzed transcripts, 4 were found to exhibit significantly different expression levels between the transplant patients and control subjects; however, only the ACD gene was sufficiently specific for telomere homeostasis.…”

“…In stage 1 of the study, the expression profiles of 123 transcripts, which represented 70 genes involved in telomere maintenance, were selected as described by Witkowska et al (21) and assessed in peripheral mononuclear blood cells (PBMCs) from representatives of the study and control groups using an oligonucleotide microarray technique (HG-U133A array; Affymetrix, Inc., Santa Clara, CA, USA).…”

“…Based on the results of the stage 1 microarray analysis and current knowledge regarding the effect of immortalization factors on telomere maintenance (9,(15)(16)(17)21), three mRNAs were selected for RT-qPCR analysis in stage 2 of the study: i) hTERT, which encodes a catalytic subunit of telomerase and component of the hTERT complex (16); ii) ACD, also referred to as telomere binding protein TPP1, which encodes one of the six core proteins of the telosome, mediates the access of telomerase to the telomere and regulates telomerase enzymatic activity; and iii) DKC1 (dyskeratosis congenita 1 or dyskerin), a member of the small nucleolar ribonucleoprotein gene family and component of the hTR subunit complex.…”