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

Regulation of the cell cycle in the ...

Clark, Jennifer Anne.

FindBook

Google Book

Amazon

博客來

Regulation of the cell cycle in the intestinal epithelium.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Regulation of the cell cycle in the intestinal epithelium./
作者:	Clark, Jennifer Anne.
面頁冊數:	183 p.
附註:	Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1107.
Contained By:	Dissertation Abstracts International65-03B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125701
ISBN:	049672990X

Regulation of the cell cycle in the intestinal epithelium.
Clark, Jennifer Anne.

Regulation of the cell cycle in the intestinal epithelium. - 183 p.

Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1107.

Thesis (Ph.D.)--State University of New York at Buffalo, 2004.

Accumulating evidence points to a role for protein kinase C (PKC) signaling in negative growth regulation in the intestine. Previous studies in this laboratory have shown that PKC activation in the IEC-18 immature, non-transformed rat intestinal crypt cell line results in downregulation of cyclin D1, induction of p21waf1/cip1 expression, and cell cycle withdrawal into G0 (Frey et al., 1997; 2000). The objectives of the current study were: (a) to determine the signal transduction element(s) that link PKC activation to changes in the cell cycle regulatory machinery and (b) to further define the role(s) of individual PKC family members in intestinal epithelial cell cycle regulation by testing the effects of various PKC agonists and inhibitors in the IEC-18 model system. Our studies point to a key role for PKC alpha signaling in PKC agonist-induced cell cycle withdrawal in the intestinal epithelium. Based on evidence that PKC alpha expression is abrogated early during intestinal carcinogenesis, this finding has important implications for the prevention/therapy of intestinal neoplasms. Analysis of the mechanism(s) underlying PKC-mediated cell cycle arrest in intestinal cells points to the involvement of the extracellular signal-related (ERK)/mitogen-activated protein kinase (MAPK) cascade. PKC activation in IEC-18 cells led to the rapid phosphorylation/activation of ERK1/2, and both PKC-mediated alterations in cyclin D1 and p21waf1/cip1 expression and cell cycle arrest were found to be ERK/MAPK-dependent. PKC-mediated ERK1/2 activation was strong and sustained in comparison with that induced by proliferative signals (i.e., growth factors) in this system, and the growth inhibitory effects of the PKC agonist phorbol 12-myristate 13-acetate (PMA) were dominant over pro-proliferative signaling by growth factors when both agents were administered simultaneously. Comparison of the cell cycle-specific effects induced by PKC agonists which differ in their ability to sustain growth arrest in IEC-18 cells showed that maintenance of PKC-mediated cell cycle exit requires sustained activation of the ERK/MAPK pathway. The duration of PKC-mediated growth arrest was found to correlate with the extent and duration of ERK1/2 activation, which in turn correlated with the extent and duration of cyclin D1 downregulation and p21 waf1/cip1 induction. PKC signaling activated both Ras and Raf-1 in IEC-18 cells, suggesting that the PKC and ERK/MAPK pathways intersect at the level of Ras in this system. (Abstract shortened by UMI.)

ISBN: 049672990XSubjects--Topical Terms:

1017686
Biology, Cell.

Regulation of the cell cycle in the intestinal epithelium.
LDR:03463nmm 2200289 4500 001 1847393
005 20051108094520.5
008 130614s2004 eng d
020 $a 049672990X
035 $a (UnM)AAI3125701
035 $a AAI3125701
040 $a UnM $c UnM
100 1 $a Clark, Jennifer Anne. $3 1935442
245 1 0 $a Regulation of the cell cycle in the intestinal epithelium.
300 $a 183 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-03, Section: B, page: 1107.
500 $a Major Professor: Jennifer D. Black.
502 $a Thesis (Ph.D.)--State University of New York at Buffalo, 2004.
520 $a Accumulating evidence points to a role for protein kinase C (PKC) signaling in negative growth regulation in the intestine. Previous studies in this laboratory have shown that PKC activation in the IEC-18 immature, non-transformed rat intestinal crypt cell line results in downregulation of cyclin D1, induction of p21waf1/cip1 expression, and cell cycle withdrawal into G0 (Frey et al., 1997; 2000). The objectives of the current study were: (a) to determine the signal transduction element(s) that link PKC activation to changes in the cell cycle regulatory machinery and (b) to further define the role(s) of individual PKC family members in intestinal epithelial cell cycle regulation by testing the effects of various PKC agonists and inhibitors in the IEC-18 model system. Our studies point to a key role for PKC alpha signaling in PKC agonist-induced cell cycle withdrawal in the intestinal epithelium. Based on evidence that PKC alpha expression is abrogated early during intestinal carcinogenesis, this finding has important implications for the prevention/therapy of intestinal neoplasms. Analysis of the mechanism(s) underlying PKC-mediated cell cycle arrest in intestinal cells points to the involvement of the extracellular signal-related (ERK)/mitogen-activated protein kinase (MAPK) cascade. PKC activation in IEC-18 cells led to the rapid phosphorylation/activation of ERK1/2, and both PKC-mediated alterations in cyclin D1 and p21waf1/cip1 expression and cell cycle arrest were found to be ERK/MAPK-dependent. PKC-mediated ERK1/2 activation was strong and sustained in comparison with that induced by proliferative signals (i.e., growth factors) in this system, and the growth inhibitory effects of the PKC agonist phorbol 12-myristate 13-acetate (PMA) were dominant over pro-proliferative signaling by growth factors when both agents were administered simultaneously. Comparison of the cell cycle-specific effects induced by PKC agonists which differ in their ability to sustain growth arrest in IEC-18 cells showed that maintenance of PKC-mediated cell cycle exit requires sustained activation of the ERK/MAPK pathway. The duration of PKC-mediated growth arrest was found to correlate with the extent and duration of ERK1/2 activation, which in turn correlated with the extent and duration of cyclin D1 downregulation and p21 waf1/cip1 induction. PKC signaling activated both Ras and Raf-1 in IEC-18 cells, suggesting that the PKC and ERK/MAPK pathways intersect at the level of Ras in this system. (Abstract shortened by UMI.)
590 $a School code: 0656.
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0379
690 $a 0307
690 $a 0992
710 2 0 $a State University of New York at Buffalo. $3 1017814
773 0 $t Dissertation Abstracts International $g 65-03B.
790 1 0 $a Black, Jennifer D., $e advisor
790 $a 0656
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3125701