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Bioinformatic analysis ofp53 respons...

Krivokrysenko, Vadim.

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Bioinformatic analysis ofp53 response in vivo.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Bioinformatic analysis ofp53 response in vivo./
作者:	Krivokrysenko, Vadim.
面頁冊數:	174 p.
附註:	Adviser: Andrei Gudkov.
Contained By:	Dissertation Abstracts International64-03B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3083947

Bioinformatic analysis ofp53 response in vivo.
Krivokrysenko, Vadim.

Bioinformatic analysis ofp53 response in vivo. - 174 p.

Adviser: Andrei Gudkov.

Thesis (Ph.D.)--University of Illinois at Chicago, Health Sciences Center, 2003.

In order to discover novel functions of p53, we identified by microarray hybridization the p53-regulated genes in human and mouse cells of different p53 status and tissue origin.Subjects--Topical Terms:

1017730
Biology, Genetics.

Bioinformatic analysis ofp53 response in vivo.
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100 1 $a Krivokrysenko, Vadim. $3 1251086
245 1 0 $a Bioinformatic analysis ofp53 response in vivo.
300 $a 174 p.
500 $a Adviser: Andrei Gudkov.
500 $a Source: Dissertation Abstracts International, Volume: 64-03, Section: B, page: 1069.
502 $a Thesis (Ph.D.)--University of Illinois at Chicago, Health Sciences Center, 2003.
520 $a In order to discover novel functions of p53, we identified by microarray hybridization the p53-regulated genes in human and mouse cells of different p53 status and tissue origin.
520 $a p53 is a tumor suppressor protein that transmits stress response stimuli to the cell fate control mechanisms. It is a transcription factor that acts primarily through activation or repression of its target genes.
520 $a Several of the new p53-activated genes encode known secreted growth inhibitory factors. This suggests that p53 can cause “bystander effect” by inducing export of growth suppressive stimuli from damaged cells to neighboring cells. Consistently, after gamma irradiation a p53-dependent accumulation of growth inhibitory factors was observed in the cell culture media and in the urine of irradiated mice. This indicates a previously unknown role for normal cells in chemo- and radiation therapy of cancer.
520 $a Among p53-repressible genes in prostate cell line LNCaP we found prostate-specific antigen (PSA) that is broadly used for early diagnostics of prostate cancer. wt p53 strongly repressed, while dominant negative p53 mutants stimulated PSA promoter driven transcription and secretion of PSA. These findings helped to explain the upregulation of PSA in prostate tumors and lead us to an idea to look for new “PSA-like” tumor markers among the genes that are downregulated by tumor suppressors.
520 $a We designed an extensive program of identification of such marker genes. Firstly, mice deficient in tumor suppressor (<italic>p53, PTEN pRB</italic>) function in prostate were analyzed by microarray hybridization. Tumor suppressor-repressed genes were identified, and their human homologs were selected as potential markers. Secondly, EST database mining was used to select genes whose expression pattern satisfied reliability and specificity criteria required of diagnostic markers. cDNA microarray carrying the candidate genes was screened with probes derived from cells of normal prostate, prostate tumor and other origin. Genes with prostate tumor-specific expression were further validated by hybridization with tissue microarrays containing the specimens of normal prostate and prostate cancer at various stages of progression. <italic>EP14</italic>, a novel transcript, was identified by our approach and found to have a prostate tumor-specific expression pattern similar to such of PSA, but with lower expression in normal prostate.
590 $a School code: 0806.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Oncology. $3 1018566
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710 2 0 $a University of Illinois at Chicago, Health Sciences Center. $3 1021703
773 0 $t Dissertation Abstracts International $g 64-03B.
790 $a 0806
790 1 0 $a Gudkov, Andrei, $e advisor
791 $a Ph.D.
792 $a 2003
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