Effect of PTTG on endogenous gene expression in HEK 293 cells

<p>Abstract</p> <p>Background</p> <p>Pituitary tumor transforming gene (PTTG), also known as securin, is highly expressed in various tumors including pituitary, thyroid, colon, ovary, testis, lung, and breast. An overexpression of PTTG enhances cell proliferation, induc...

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Main Authors: Panguluri Siva K, Kakar Sham S
Format: Article
Language:English
Published: BMC 2009-12-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/10/577
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author Panguluri Siva K
Kakar Sham S
author_facet Panguluri Siva K
Kakar Sham S
author_sort Panguluri Siva K
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Pituitary tumor transforming gene (PTTG), also known as securin, is highly expressed in various tumors including pituitary, thyroid, colon, ovary, testis, lung, and breast. An overexpression of PTTG enhances cell proliferation, induces cellular transformation <it>in vitro</it>, and promotes tumor development in nude mice. PTTG also inhibits separation of sister chromatids leading to aneuploidy and genetic instability. A great amount of work has been undertaken to understand the biology of PTTG and its expression in various tumors. However, mechanisms by which PTTG mediates its tumorigenic function are not fully understood. To utilize this gene for cancer therapy, identification of the downstream signaling genes regulated by PTTG in mediation of its tumorigenic function is necessary. For this purpose, we expressed PTTG in human embryonic kidney (HEK293) cells that do not express PTTG and analyzed the downstream genes using microarray analysis.</p> <p>Results</p> <p>A total of 22,277 genes printed on an Affymetrix HG-U133A 2.0 GeneChip™ array were screened with labeled cRNA prepared from HEK293 cells infected with adenovirus vector expressing PTTG cDNA (AdPTTG cDNA) and compared with labeled cRNA prepared from HEK293 cells infected with control adenovirus (control Ad) or adenovirus vector expressing GFP (AdGFP). Out of 22,277 genes, 71 genes were down-regulated and 35 genes were up-regulated with an FDR corrected p-value of ≤ 0.05 and a fold change of ≥2. Most of the altered genes identified are involved in the cell cycle and cell apoptosis; a few are involved in mRNA processing and nitrogen metabolism. Most of the up-regulated genes belong to the histone protein family.</p> <p>Conclusion</p> <p>PTTG is a well-studied oncogene for its role in tumorigenesis. In addition to its importance in regulation of the cell cycle, this gene has also been recently shown to play a role in the induction of cell apoptosis. The microarray analysis in the present study demonstrated that PTTG may induce apoptosis by down-regulation of oncogenes such as v-Jun and v-maf and up-regulation of the histone family of genes.</p>
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spelling doaj.art-097cd03e841944cd9e4bec598071f3362022-12-22T00:35:43ZengBMCBMC Genomics1471-21642009-12-0110157710.1186/1471-2164-10-577Effect of PTTG on endogenous gene expression in HEK 293 cellsPanguluri Siva KKakar Sham S<p>Abstract</p> <p>Background</p> <p>Pituitary tumor transforming gene (PTTG), also known as securin, is highly expressed in various tumors including pituitary, thyroid, colon, ovary, testis, lung, and breast. An overexpression of PTTG enhances cell proliferation, induces cellular transformation <it>in vitro</it>, and promotes tumor development in nude mice. PTTG also inhibits separation of sister chromatids leading to aneuploidy and genetic instability. A great amount of work has been undertaken to understand the biology of PTTG and its expression in various tumors. However, mechanisms by which PTTG mediates its tumorigenic function are not fully understood. To utilize this gene for cancer therapy, identification of the downstream signaling genes regulated by PTTG in mediation of its tumorigenic function is necessary. For this purpose, we expressed PTTG in human embryonic kidney (HEK293) cells that do not express PTTG and analyzed the downstream genes using microarray analysis.</p> <p>Results</p> <p>A total of 22,277 genes printed on an Affymetrix HG-U133A 2.0 GeneChip™ array were screened with labeled cRNA prepared from HEK293 cells infected with adenovirus vector expressing PTTG cDNA (AdPTTG cDNA) and compared with labeled cRNA prepared from HEK293 cells infected with control adenovirus (control Ad) or adenovirus vector expressing GFP (AdGFP). Out of 22,277 genes, 71 genes were down-regulated and 35 genes were up-regulated with an FDR corrected p-value of ≤ 0.05 and a fold change of ≥2. Most of the altered genes identified are involved in the cell cycle and cell apoptosis; a few are involved in mRNA processing and nitrogen metabolism. Most of the up-regulated genes belong to the histone protein family.</p> <p>Conclusion</p> <p>PTTG is a well-studied oncogene for its role in tumorigenesis. In addition to its importance in regulation of the cell cycle, this gene has also been recently shown to play a role in the induction of cell apoptosis. The microarray analysis in the present study demonstrated that PTTG may induce apoptosis by down-regulation of oncogenes such as v-Jun and v-maf and up-regulation of the histone family of genes.</p>http://www.biomedcentral.com/1471-2164/10/577
spellingShingle Panguluri Siva K
Kakar Sham S
Effect of PTTG on endogenous gene expression in HEK 293 cells
BMC Genomics
title Effect of PTTG on endogenous gene expression in HEK 293 cells
title_full Effect of PTTG on endogenous gene expression in HEK 293 cells
title_fullStr Effect of PTTG on endogenous gene expression in HEK 293 cells
title_full_unstemmed Effect of PTTG on endogenous gene expression in HEK 293 cells
title_short Effect of PTTG on endogenous gene expression in HEK 293 cells
title_sort effect of pttg on endogenous gene expression in hek 293 cells
url http://www.biomedcentral.com/1471-2164/10/577
work_keys_str_mv AT pangulurisivak effectofpttgonendogenousgeneexpressioninhek293cells
AT kakarshams effectofpttgonendogenousgeneexpressioninhek293cells