Downregulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2 in non-small cell lung cancer
Chromosomal and genome abnormalities of 3p are frequent in many epithelial tumors, including lung cancer. Several critical regions with a high frequency of hemi-and homozygous deletions in tumors are known for 3p, and more than 20 cancer-related genes occur in 3p21.3. Quantitative real-time PCR was...
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creator | Anedchenko, E. A Dmitriev, A. A Krasnov, G. S Kondrat'eva, O. O Kopantsev, E. P Vinogradova, T. V Zinov'eva, M. V Zborovskaya, I. B Polotsky, B. E Sacharova, O. V Kashuba, V. I Zabarovsky, E. R Senchenko, V. N |
description | Chromosomal and genome abnormalities of 3p are frequent in many epithelial tumors, including lung cancer. Several critical regions with a high frequency of hemi-and homozygous deletions in tumors are known for 3p, and more than 20 cancer-related genes occur in 3p21.3. Quantitative real-time PCR was used to measure the mRNA level for tumor-suppressor and candidate genes of 3p21.3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2) in major types of non-small cell lung cancer (NSCLC): squamous cell lung cancer (SCC) and lung adenocarcinoma (AC). A significant (2-to 100-fold) and frequent (44-100%) decrease in mRNA levels was observed in NSCLC. The mRNA level decrease and its frequency depended on the histological type of NSCLC for all genes. The downregulation of RASSF1A and ITGA9 was significantly associated with AC progression; the same tendency was observed for RBSP3/CTDSPL, NPRL2/G21, HYAL1, and HYAL2. In SCC, the downregulation of all genes was not associated with the clinical stage, tumor cells differentiation, and metastasis in lymph nodes. The RBSP3/CTDSPL, NPRL2/G21, ITGA9, HYAL1, and HYAL2 mRNA levels significantly (5-to 13-fold on average) decreased at a high frequency (83-100%) as early as SCC stage I. Simultaneous downregulation of all six genes was observed in some tumor samples and was independent of the gene position in 3p21.3 and the functions of the protein products. The Spearman correlation coefficient r s was 0.63-0.91, p < 0.001. The highest r s values were obtained for gene pairs ITGA9-HYAL2 and HYAL1-HYAL2, whose products mediate cell-cell adhesion and cell-matrix interactions; coregulation of the genes was assumed on this basis. Both genetic and epigenetic mechanisms proved to be important for downregulation of RBSP3/CTDSPL and ITGA9. This finding supported the hypothesis that the cluster of cancerrelated genes in the extended 3p21.3 locus is simultaneously inactivated during the development and progression of lung cancer and other epithelial tumors. A significant and frequent decrease in the mRNA level of the six genes in SCC could be important for developing specific biomarker sets for early SCC diagnosis and new approaches to gene therapy of NSCLC. |
doi_str_mv | 10.1134/S0026893308060058 |
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A ; Dmitriev, A. A ; Krasnov, G. S ; Kondrat'eva, O. O ; Kopantsev, E. P ; Vinogradova, T. V ; Zinov'eva, M. V ; Zborovskaya, I. B ; Polotsky, B. E ; Sacharova, O. V ; Kashuba, V. I ; Zabarovsky, E. R ; Senchenko, V. N</creator><creatorcontrib>Anedchenko, E. A ; Dmitriev, A. A ; Krasnov, G. S ; Kondrat'eva, O. O ; Kopantsev, E. P ; Vinogradova, T. V ; Zinov'eva, M. V ; Zborovskaya, I. B ; Polotsky, B. E ; Sacharova, O. V ; Kashuba, V. I ; Zabarovsky, E. R ; Senchenko, V. N</creatorcontrib><description>Chromosomal and genome abnormalities of 3p are frequent in many epithelial tumors, including lung cancer. Several critical regions with a high frequency of hemi-and homozygous deletions in tumors are known for 3p, and more than 20 cancer-related genes occur in 3p21.3. Quantitative real-time PCR was used to measure the mRNA level for tumor-suppressor and candidate genes of 3p21.3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2) in major types of non-small cell lung cancer (NSCLC): squamous cell lung cancer (SCC) and lung adenocarcinoma (AC). A significant (2-to 100-fold) and frequent (44-100%) decrease in mRNA levels was observed in NSCLC. The mRNA level decrease and its frequency depended on the histological type of NSCLC for all genes. The downregulation of RASSF1A and ITGA9 was significantly associated with AC progression; the same tendency was observed for RBSP3/CTDSPL, NPRL2/G21, HYAL1, and HYAL2. In SCC, the downregulation of all genes was not associated with the clinical stage, tumor cells differentiation, and metastasis in lymph nodes. The RBSP3/CTDSPL, NPRL2/G21, ITGA9, HYAL1, and HYAL2 mRNA levels significantly (5-to 13-fold on average) decreased at a high frequency (83-100%) as early as SCC stage I. Simultaneous downregulation of all six genes was observed in some tumor samples and was independent of the gene position in 3p21.3 and the functions of the protein products. The Spearman correlation coefficient r s was 0.63-0.91, p < 0.001. The highest r s values were obtained for gene pairs ITGA9-HYAL2 and HYAL1-HYAL2, whose products mediate cell-cell adhesion and cell-matrix interactions; coregulation of the genes was assumed on this basis. Both genetic and epigenetic mechanisms proved to be important for downregulation of RBSP3/CTDSPL and ITGA9. This finding supported the hypothesis that the cluster of cancerrelated genes in the extended 3p21.3 locus is simultaneously inactivated during the development and progression of lung cancer and other epithelial tumors. A significant and frequent decrease in the mRNA level of the six genes in SCC could be important for developing specific biomarker sets for early SCC diagnosis and new approaches to gene therapy of NSCLC.</description><identifier>ISSN: 0026-8933</identifier><identifier>EISSN: 1608-3245</identifier><identifier>DOI: 10.1134/S0026893308060058</identifier><language>eng</language><publisher>Dordrecht: Dordrecht : SP MAIK Nauka/Interperiodica</publisher><subject>Biochemistry ; Biomarkers ; Biomedical and Life Sciences ; Chromosomes ; Gene expression ; Genomics. Transcriptomics. Proteomics ; Human Genetics ; Life Sciences ; Lung cancer ; Medicin och hälsovetenskap ; Molecular biology</subject><ispartof>Molecular biology (New York), 2008-12, Vol.42 (6), p.859-869</ispartof><rights>MAIK Nauka 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-162761d58933f5f5d988da9f88e4ca0f5839db74c1320b861dd9264e73953b773</citedby><cites>FETCH-LOGICAL-c427t-162761d58933f5f5d988da9f88e4ca0f5839db74c1320b861dd9264e73953b773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1134/S0026893308060058$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1134/S0026893308060058$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,315,781,785,886,27925,27926,41489,42558,51320</link.rule.ids><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:118012171$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Anedchenko, E. A</creatorcontrib><creatorcontrib>Dmitriev, A. A</creatorcontrib><creatorcontrib>Krasnov, G. S</creatorcontrib><creatorcontrib>Kondrat'eva, O. O</creatorcontrib><creatorcontrib>Kopantsev, E. P</creatorcontrib><creatorcontrib>Vinogradova, T. V</creatorcontrib><creatorcontrib>Zinov'eva, M. V</creatorcontrib><creatorcontrib>Zborovskaya, I. B</creatorcontrib><creatorcontrib>Polotsky, B. E</creatorcontrib><creatorcontrib>Sacharova, O. V</creatorcontrib><creatorcontrib>Kashuba, V. I</creatorcontrib><creatorcontrib>Zabarovsky, E. R</creatorcontrib><creatorcontrib>Senchenko, V. N</creatorcontrib><title>Downregulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2 in non-small cell lung cancer</title><title>Molecular biology (New York)</title><addtitle>Mol Biol</addtitle><description>Chromosomal and genome abnormalities of 3p are frequent in many epithelial tumors, including lung cancer. Several critical regions with a high frequency of hemi-and homozygous deletions in tumors are known for 3p, and more than 20 cancer-related genes occur in 3p21.3. Quantitative real-time PCR was used to measure the mRNA level for tumor-suppressor and candidate genes of 3p21.3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2) in major types of non-small cell lung cancer (NSCLC): squamous cell lung cancer (SCC) and lung adenocarcinoma (AC). A significant (2-to 100-fold) and frequent (44-100%) decrease in mRNA levels was observed in NSCLC. The mRNA level decrease and its frequency depended on the histological type of NSCLC for all genes. The downregulation of RASSF1A and ITGA9 was significantly associated with AC progression; the same tendency was observed for RBSP3/CTDSPL, NPRL2/G21, HYAL1, and HYAL2. In SCC, the downregulation of all genes was not associated with the clinical stage, tumor cells differentiation, and metastasis in lymph nodes. The RBSP3/CTDSPL, NPRL2/G21, ITGA9, HYAL1, and HYAL2 mRNA levels significantly (5-to 13-fold on average) decreased at a high frequency (83-100%) as early as SCC stage I. Simultaneous downregulation of all six genes was observed in some tumor samples and was independent of the gene position in 3p21.3 and the functions of the protein products. The Spearman correlation coefficient r s was 0.63-0.91, p < 0.001. The highest r s values were obtained for gene pairs ITGA9-HYAL2 and HYAL1-HYAL2, whose products mediate cell-cell adhesion and cell-matrix interactions; coregulation of the genes was assumed on this basis. Both genetic and epigenetic mechanisms proved to be important for downregulation of RBSP3/CTDSPL and ITGA9. This finding supported the hypothesis that the cluster of cancerrelated genes in the extended 3p21.3 locus is simultaneously inactivated during the development and progression of lung cancer and other epithelial tumors. A significant and frequent decrease in the mRNA level of the six genes in SCC could be important for developing specific biomarker sets for early SCC diagnosis and new approaches to gene therapy of NSCLC.</description><subject>Biochemistry</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Chromosomes</subject><subject>Gene expression</subject><subject>Genomics. Transcriptomics. 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Several critical regions with a high frequency of hemi-and homozygous deletions in tumors are known for 3p, and more than 20 cancer-related genes occur in 3p21.3. Quantitative real-time PCR was used to measure the mRNA level for tumor-suppressor and candidate genes of 3p21.3 (RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2) in major types of non-small cell lung cancer (NSCLC): squamous cell lung cancer (SCC) and lung adenocarcinoma (AC). A significant (2-to 100-fold) and frequent (44-100%) decrease in mRNA levels was observed in NSCLC. The mRNA level decrease and its frequency depended on the histological type of NSCLC for all genes. The downregulation of RASSF1A and ITGA9 was significantly associated with AC progression; the same tendency was observed for RBSP3/CTDSPL, NPRL2/G21, HYAL1, and HYAL2. In SCC, the downregulation of all genes was not associated with the clinical stage, tumor cells differentiation, and metastasis in lymph nodes. The RBSP3/CTDSPL, NPRL2/G21, ITGA9, HYAL1, and HYAL2 mRNA levels significantly (5-to 13-fold on average) decreased at a high frequency (83-100%) as early as SCC stage I. Simultaneous downregulation of all six genes was observed in some tumor samples and was independent of the gene position in 3p21.3 and the functions of the protein products. The Spearman correlation coefficient r s was 0.63-0.91, p < 0.001. The highest r s values were obtained for gene pairs ITGA9-HYAL2 and HYAL1-HYAL2, whose products mediate cell-cell adhesion and cell-matrix interactions; coregulation of the genes was assumed on this basis. Both genetic and epigenetic mechanisms proved to be important for downregulation of RBSP3/CTDSPL and ITGA9. This finding supported the hypothesis that the cluster of cancerrelated genes in the extended 3p21.3 locus is simultaneously inactivated during the development and progression of lung cancer and other epithelial tumors. A significant and frequent decrease in the mRNA level of the six genes in SCC could be important for developing specific biomarker sets for early SCC diagnosis and new approaches to gene therapy of NSCLC.</abstract><cop>Dordrecht</cop><pub>Dordrecht : SP MAIK Nauka/Interperiodica</pub><doi>10.1134/S0026893308060058</doi><tpages>11</tpages></addata></record> |
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subjects | Biochemistry Biomarkers Biomedical and Life Sciences Chromosomes Gene expression Genomics. Transcriptomics. Proteomics Human Genetics Life Sciences Lung cancer Medicin och hälsovetenskap Molecular biology |
title | Downregulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1, and HYAL2 in non-small cell lung cancer |
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