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Steroid receptor coactivator AIB1 re...

Lahusen, John Tyler.

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Steroid receptor coactivator AIB1 regulates EGFR phosphorylation and signaling in cancer.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Steroid receptor coactivator AIB1 regulates EGFR phosphorylation and signaling in cancer./
Author:	Lahusen, John Tyler.
Description:	177 p.
Notes:	Adviser: Anna T. Reigel.
Contained By:	Dissertation Abstracts International68-07B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3270686
ISBN:	9780549101796

Steroid receptor coactivator AIB1 regulates EGFR phosphorylation and signaling in cancer.
Lahusen, John Tyler.

Steroid receptor coactivator AIB1 regulates EGFR phosphorylation and signaling in cancer. - 177 p.

Adviser: Anna T. Reigel.

Thesis (Ph.D.)--Georgetown University Medical Center, 2007.

AIB1 (Amplified in Breast Cancer 1) is a member of the p160 steroid receptor coactivator family, including SRC-1 and TIF2, which enhance transcriptional activity of nuclear receptors and other transcription factors. Amplification and/or overexpression of AIB1 correlates with progression of multiple human epithelial cancers. Additionally, overexpression of AIB1 in mice leads to formation of tumors of the mammary gland and other organs through its modulation of both steroid and growth factor signaling. Specifically, AIB1 levels are limiting for insulin-like growth factor-1 and Ras signaling, but its role in other growth factor pathways is not known. Epidermal growth factor receptor (EGFR)/HER1 is a critical factor in the development of most epithelial tumors through its promotion of growth, metastasis, and angiogenesis. It is a member of the HER family of receptor tyrosine kinases, which is activated upon binding to its ligands such as EGF or transforming growth factor-alpha. In this study, it was determined if the oncogenic effects of AIB1 could be explained by control of the EGFR pathway. AIB1 was shown to regulate the level of tyrosine phosphorylation of EGFR and its signaling capacity. Knockdown of AIB1 in multiple cancer cell lines resulted in reduced EGF-induced phosphorylation of EGFR on multiple tyrosine residues with no change in EGFR expression. Regulation of phosphorylation was due in part to a phosphatase-dependent mechanism that specifically targets EGFR and not other receptor tyrosine kinases. This resulted in decreased activation of extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 5 (STAT5), and c-Jun NH 2-terminal kinase (JNK1/2). As a biological response to a knockdown in AIB1 levels, there was a reduction in EGF-stimulated proliferation of A549 lung cancer and MDA-MB-231 breast cancer cells. These results suggest that AIB1 regulates EGFR-dependent signaling and biological responses in human cancer cells by modulating the level of EGFR tyrosine phosphorylation.

ISBN: 9780549101796Subjects--Topical Terms:

1017719
Biology, Molecular.

Steroid receptor coactivator AIB1 regulates EGFR phosphorylation and signaling in cancer.
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020 $a 9780549101796
035 $a (UMI)AAI3270686
035 $a AAI3270686
040 $a UMI $c UMI
100 1 $a Lahusen, John Tyler. $3 1267721
245 1 0 $a Steroid receptor coactivator AIB1 regulates EGFR phosphorylation and signaling in cancer.
300 $a 177 p.
500 $a Adviser: Anna T. Reigel.
500 $a Source: Dissertation Abstracts International, Volume: 68-07, Section: B, page: 4274.
502 $a Thesis (Ph.D.)--Georgetown University Medical Center, 2007.
520 $a AIB1 (Amplified in Breast Cancer 1) is a member of the p160 steroid receptor coactivator family, including SRC-1 and TIF2, which enhance transcriptional activity of nuclear receptors and other transcription factors. Amplification and/or overexpression of AIB1 correlates with progression of multiple human epithelial cancers. Additionally, overexpression of AIB1 in mice leads to formation of tumors of the mammary gland and other organs through its modulation of both steroid and growth factor signaling. Specifically, AIB1 levels are limiting for insulin-like growth factor-1 and Ras signaling, but its role in other growth factor pathways is not known. Epidermal growth factor receptor (EGFR)/HER1 is a critical factor in the development of most epithelial tumors through its promotion of growth, metastasis, and angiogenesis. It is a member of the HER family of receptor tyrosine kinases, which is activated upon binding to its ligands such as EGF or transforming growth factor-alpha. In this study, it was determined if the oncogenic effects of AIB1 could be explained by control of the EGFR pathway. AIB1 was shown to regulate the level of tyrosine phosphorylation of EGFR and its signaling capacity. Knockdown of AIB1 in multiple cancer cell lines resulted in reduced EGF-induced phosphorylation of EGFR on multiple tyrosine residues with no change in EGFR expression. Regulation of phosphorylation was due in part to a phosphatase-dependent mechanism that specifically targets EGFR and not other receptor tyrosine kinases. This resulted in decreased activation of extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 5 (STAT5), and c-Jun NH 2-terminal kinase (JNK1/2). As a biological response to a knockdown in AIB1 levels, there was a reduction in EGF-stimulated proliferation of A549 lung cancer and MDA-MB-231 breast cancer cells. These results suggest that AIB1 regulates EGFR-dependent signaling and biological responses in human cancer cells by modulating the level of EGFR tyrosine phosphorylation.
590 $a School code: 0544.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0307
690 $a 0992
710 2 $a Georgetown University Medical Center. $3 1021821
773 0 $t Dissertation Abstracts International $g 68-07B.
790 $a 0544
790 1 0 $a Reigel, Anna T., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3270686