東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Post-transcriptional regulation and ...

Kim, Kwang-Hee (Marianne).

FindBook

Google Book

Amazon

博客來

Post-transcriptional regulation and autoregulation of the N-myc gene in neuroblastoma.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Post-transcriptional regulation and autoregulation of the N-myc gene in neuroblastoma./
作者:	Kim, Kwang-Hee (Marianne).
面頁冊數:	79 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6023.
Contained By:	Dissertation Abstracts International64-12B.
標題:	Health Sciences, Oncology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3115445

Post-transcriptional regulation and autoregulation of the N-myc gene in neuroblastoma.
Kim, Kwang-Hee (Marianne).

Post-transcriptional regulation and autoregulation of the N-myc gene in neuroblastoma. - 79 p.

Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6023.

Thesis (Ph.D.)--Mount Sinai School of Medicine of New York University, 2004.

The Myc family of oncogenes is involved in the genesis of many human cancers and amplification of one member, N-<italic>myc</italic>, is associated with a poor prognosis in the common childhood tumor neuroblastoma. Our laboratory has focused on post-transcriptional regulation of the N-<italic>myc</italic> gene through a unique region identified in intron 1, the Tissue Specific Element (TSE), as well as an autoregulatory pathway, whereby N-<italic>myc</italic> is regulated at the transcriptional level in a negative feedback loop. The first part of these studies describes preliminary data related to post-transcriptional regulation of the N-<italic>myc</italic> gene through the TSE. Mutation and deletion constructs of the TSE were made to better understand the mechanism of TSE action and to isolate TSE binding proteins. The second part of the studies was focused on elucidating N-<italic>myc</italic> autoregulatory mechanism. Previous observations indicated that N-myc autoregulation was disrupted in amplified neuroblastoma cell lines, but intact in single copy cell lines. However, in these studies the autoregulatory circuit is proved to be operative even in amplified cell lines. Based on the literature of c-<italic>myc</italic> regulation and our previous cDNA microarray data, several candidate genes—Mxi1 (Mad2), c-<italic>myc</italic> promoter binding protein (MBP-1), a c-Myc-interacting zinc finger protein (Miz), and HDAC2 (historic deacetylase 2) were evaluated for their involvement in N-<italic>myc</italic> autoregulation. In summary, Mxi1 showed consistently a modest effect in down-regulating the N-<italic> myc</italic> promoter in transient reporter assays. Expression of <italic> c-myc, Mxi1</italic>, and <italic>mHDAC2</italic> genes resulted in a 3–4 fold decrease in endogenous N-<italic>myc</italic> level. <italic>Mxi1</italic> and <italic>HDAC2</italic> were up-regulated by N-Myc in a <italic>myc</italic>-inducible cell line and N-<italic>myc</italic> expressing cell lines. In addition, the down-regulation of the N-<italic>myc</italic> promoter was relieved in the presence of trichostatin A. Furthermore, increased association of HDAC2 with the N-<italic>myc</italic> promoter by chromatin immunoprecipitation was observed upon down-regulation of endogenous N-<italic>myc</italic>. In conclusion, these studies show that the autoregulatory circuit is intact in both amplified and single copy neuroblastoma cell lines, higher levels of trans-acting factors are needed to down-regulate N-<italic>myc</italic> expression in amplified cell lines, and HDAC2 is involved in N-<italic>myc</italic> autoregulatory pathway.Subjects--Topical Terms:

1018566
Health Sciences, Oncology.

Post-transcriptional regulation and autoregulation of the N-myc gene in neuroblastoma.
LDR:03573nmm 2200265 4500 001 1856200
005 20040621100422.5
008 130614s2004 eng d
035 $a (UnM)AAI3115445
035 $a AAI3115445
040 $a UnM $c UnM
100 1 $a Kim, Kwang-Hee (Marianne). $3 1943984
245 1 0 $a Post-transcriptional regulation and autoregulation of the N-myc gene in neuroblastoma.
300 $a 79 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6023.
500 $a Adviser: William L. Carroll.
502 $a Thesis (Ph.D.)--Mount Sinai School of Medicine of New York University, 2004.
520 $a The Myc family of oncogenes is involved in the genesis of many human cancers and amplification of one member, N-<italic>myc</italic>, is associated with a poor prognosis in the common childhood tumor neuroblastoma. Our laboratory has focused on post-transcriptional regulation of the N-<italic>myc</italic> gene through a unique region identified in intron 1, the Tissue Specific Element (TSE), as well as an autoregulatory pathway, whereby N-<italic>myc</italic> is regulated at the transcriptional level in a negative feedback loop. The first part of these studies describes preliminary data related to post-transcriptional regulation of the N-<italic>myc</italic> gene through the TSE. Mutation and deletion constructs of the TSE were made to better understand the mechanism of TSE action and to isolate TSE binding proteins. The second part of the studies was focused on elucidating N-<italic>myc</italic> autoregulatory mechanism. Previous observations indicated that N-myc autoregulation was disrupted in amplified neuroblastoma cell lines, but intact in single copy cell lines. However, in these studies the autoregulatory circuit is proved to be operative even in amplified cell lines. Based on the literature of c-<italic>myc</italic> regulation and our previous cDNA microarray data, several candidate genes—Mxi1 (Mad2), c-<italic>myc</italic> promoter binding protein (MBP-1), a c-Myc-interacting zinc finger protein (Miz), and HDAC2 (historic deacetylase 2) were evaluated for their involvement in N-<italic>myc</italic> autoregulation. In summary, Mxi1 showed consistently a modest effect in down-regulating the N-<italic> myc</italic> promoter in transient reporter assays. Expression of <italic> c-myc, Mxi1</italic>, and <italic>mHDAC2</italic> genes resulted in a 3–4 fold decrease in endogenous N-<italic>myc</italic> level. <italic>Mxi1</italic> and <italic>HDAC2</italic> were up-regulated by N-Myc in a <italic>myc</italic>-inducible cell line and N-<italic>myc</italic> expressing cell lines. In addition, the down-regulation of the N-<italic>myc</italic> promoter was relieved in the presence of trichostatin A. Furthermore, increased association of HDAC2 with the N-<italic>myc</italic> promoter by chromatin immunoprecipitation was observed upon down-regulation of endogenous N-<italic>myc</italic>. In conclusion, these studies show that the autoregulatory circuit is intact in both amplified and single copy neuroblastoma cell lines, higher levels of trans-acting factors are needed to down-regulate N-<italic>myc</italic> expression in amplified cell lines, and HDAC2 is involved in N-<italic>myc</italic> autoregulatory pathway.
590 $a School code: 1353.
650 4 $a Health Sciences, Oncology. $3 1018566
650 4 $a Biology, Molecular. $3 1017719
690 $a 0992
690 $a 0307
710 2 0 $a Mount Sinai School of Medicine of New York University. $3 1025278
773 0 $t Dissertation Abstracts International $g 64-12B.
790 1 0 $a Carroll, William L., $e advisor
790 $a 1353
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3115445