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Growth factor-mediated telomerase ac...

Bermudez, Yira.

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Growth factor-mediated telomerase activity in ovarian cancer cells.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Growth factor-mediated telomerase activity in ovarian cancer cells./
Author:	Bermudez, Yira.
Description:	169 p.
Notes:	Adviser: Patricia A. Kruk.
Contained By:	Dissertation Abstracts International68-04B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3260043

Growth factor-mediated telomerase activity in ovarian cancer cells.
Bermudez, Yira.

Growth factor-mediated telomerase activity in ovarian cancer cells. - 169 p.

Adviser: Patricia A. Kruk.

Thesis (Ph.D.)--University of South Florida, 2007.

Ovarian cancer is the leading cause of gynecological cancer death in the United States. Even though no single genetic alteration can be attributed to all ovarian cancers, 90% of ovarian tumors express telomerase, a ribonucleoprotein that elongates telomeric (TTAGGG)n repeats de novo. In normal somatic cells, telomerase is absent. In cancer cells, the re-expression of telomerase allows senescence to be bypassed contributing to cellular immortalization, a key step for cellular transformation, making telomerase a potentially important target for therapeutic intervention.Subjects--Topical Terms:

1017686
Biology, Cell.

Growth factor-mediated telomerase activity in ovarian cancer cells.
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035 $a (UMI)AAI3260043
035 $a AAI3260043
040 $a UMI $c UMI
100 1 $a Bermudez, Yira. $3 1263260
245 1 0 $a Growth factor-mediated telomerase activity in ovarian cancer cells.
300 $a 169 p.
500 $a Adviser: Patricia A. Kruk.
500 $a Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2269.
502 $a Thesis (Ph.D.)--University of South Florida, 2007.
520 $a Ovarian cancer is the leading cause of gynecological cancer death in the United States. Even though no single genetic alteration can be attributed to all ovarian cancers, 90% of ovarian tumors express telomerase, a ribonucleoprotein that elongates telomeric (TTAGGG)n repeats de novo. In normal somatic cells, telomerase is absent. In cancer cells, the re-expression of telomerase allows senescence to be bypassed contributing to cellular immortalization, a key step for cellular transformation, making telomerase a potentially important target for therapeutic intervention.
520 $a Ovarian cancer cells secrete vascular endothelial growth factor (VEGF) and lysophosphatidic acid (LPA) that feedback through their receptors present on ovarian cancer cells to promote cell growth. Since telomerase can be regulated by growth factors, I examined VEGF regulation of telomerase activity and the possible contribution of LPA as an upstream regulator of VEGF-mediated telomerase activity in ovarian cancer. My data reveal that both VEGF and LPA upregulate telomerase activity by ERK 1/2-dependent transcriptional activation within the -976 to the -378 bp hTERT promoter regions where Sp1 is one of the major mediators of VEGF- and LPA-induced transactivation of hTERT. It also identifies telomerase as a novel molecular target of LPA as well as a target of VEGF in non-endothelial cells. In addition I found that, vitamin E, a dietary supplement able to degrade and suppress LPA activity, consistently abrogrates LPA-mediated telomerase activity through transcriptional inhibition of the hTERT -976 to -578 bp promoter regions.
520 $a Lastly, since epidermal growth factor (EGF) promotes ovarian surface epithelial (OSE) cell growth and EGF receptors are frequently constitutively activated in ovarian cancers, the potential contribution of EGF in the regulation of telomerase activity was also examined. While none of the ovarian cancer cell lines examined produced large amounts of EGF, EGF stimulation of telomerase activity was mediated by Sp1 and c-Myc transcription factors within the hTERT core promoter in an ERK 1/2/Pyk2-dependent manner.
520 $a In conclusion, my research shows differential regulation of telomerase activity by growth factor and/or anti-oxidant nutraceuticals. In the future, these factors may be exploited as adjuvant therapy for improved chemotherapeutic benefit to decrease the mortality associated with ovarian cancer.
590 $a School code: 0206.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Health Sciences, Pathology. $3 1017854
690 $a 0379
690 $a 0571
690 $a 0992
710 2 $a University of South Florida. $3 1020446
773 0 $t Dissertation Abstracts International $g 68-04B.
790 $a 0206
790 1 0 $a Kruk, Patricia A., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3260043