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

Mechanisms underlying the link betwe...

Liu, Jehnan.

FindBook

Google Book

Amazon

博客來

Mechanisms underlying the link between obesity and neoplastic progression.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Mechanisms underlying the link between obesity and neoplastic progression./
作者:	Liu, Jehnan.
面頁冊數:	84 p.
附註:	Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3447.
Contained By:	Dissertation Abstracts International71-06B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407732
ISBN:	9781124016160

Mechanisms underlying the link between obesity and neoplastic progression.
Liu, Jehnan.

Mechanisms underlying the link between obesity and neoplastic progression. - 84 p.

Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3447.

Thesis (Ph.D.)--The University of Toledo, 2010.

The mechanistic link between prostate cancer and obesity is elusive. Pten+/-- mice with monoallelic mutation of Phosphatase and TENsin homolog (Pten), a well-characterized tumor suppressor gene, develop murine prostatic intraepithelial neoplasia (mPIN) lesions with low penetrance. We observed that protein levels of another tumor suppressor gene, the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), are elevated in our Pten +/-- mouse prostates. When Pten+/-- mice were fed with high fat diet (HF) beginning at weaning and until sacrifice at ages 4 and 7 months, they exhibited more progressive mouse prostate intraepithelial neoplasia (mPIN) lesions and significantly greater visceral obesity compared to age-matched regular chow-fed controls. With CEACAM1 being significantly reduced in metastatic prostate cancer and in obese humans, we hypothesized that global deletion of Ceacam1 would remove the protection against further progression to advanced mPIN lesions in Pten+/-- mice. High-fat intake for 6 months induced severe mPIN and invasive prostate adenocarcinoma in 21% of Pten +/-- mice whereas the penetrance was 46% for the mice with biallelic deletion of Ceacam1. At the same time, we observed a marked increase in CEACAM1 in prostate in high fat fed Pten+/-- mice compared to regular diet controls. Quantitative RT-PCR analysis showed that HF diet increases both CEACAM1 short (S) and long (L) isoforms in Pten mice leading to an S:L of 3.4 to 1. Because the tumor suppression activity of CEACAM1-L is regulated by a balanced S:L ratio, it is possible that this shift in S:L ratio by HF synergizes with Pten loss to cause a more progressive neoplastic form as compared to Pten mice on regular diet. The mechanism of this synergy between S:L imbalances and Pten loss is unclear. It could be related to (A) increased angiogenesis from endothelial CEACAM1, or (B) a dominant-negative effect on tumor suppression by the higher relative content of the short isoform in epithelial cells. Both possibilities warrant further studies. Taken together, this study suggests that lack of CEACAM1 activity potentiates neoplastic progression caused by Pten haploinsufficiency.

ISBN: 9781124016160Subjects--Topical Terms:

1017730
Biology, Genetics.

Mechanisms underlying the link between obesity and neoplastic progression.
LDR:03070nam 2200265 4500 001 1402995
005 20111108080343.5
008 130515s2010 ||||||||||||||||| ||eng d
020 $a 9781124016160
035 $a (UMI)AAI3407732
035 $a AAI3407732
040 $a UMI $c UMI
100 1 $a Liu, Jehnan. $3 1682226
245 1 0 $a Mechanisms underlying the link between obesity and neoplastic progression.
300 $a 84 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3447.
500 $a Adviser: Sonia M. Najjar.
502 $a Thesis (Ph.D.)--The University of Toledo, 2010.
520 $a The mechanistic link between prostate cancer and obesity is elusive. Pten+/-- mice with monoallelic mutation of Phosphatase and TENsin homolog (Pten), a well-characterized tumor suppressor gene, develop murine prostatic intraepithelial neoplasia (mPIN) lesions with low penetrance. We observed that protein levels of another tumor suppressor gene, the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), are elevated in our Pten +/-- mouse prostates. When Pten+/-- mice were fed with high fat diet (HF) beginning at weaning and until sacrifice at ages 4 and 7 months, they exhibited more progressive mouse prostate intraepithelial neoplasia (mPIN) lesions and significantly greater visceral obesity compared to age-matched regular chow-fed controls. With CEACAM1 being significantly reduced in metastatic prostate cancer and in obese humans, we hypothesized that global deletion of Ceacam1 would remove the protection against further progression to advanced mPIN lesions in Pten+/-- mice. High-fat intake for 6 months induced severe mPIN and invasive prostate adenocarcinoma in 21% of Pten +/-- mice whereas the penetrance was 46% for the mice with biallelic deletion of Ceacam1. At the same time, we observed a marked increase in CEACAM1 in prostate in high fat fed Pten+/-- mice compared to regular diet controls. Quantitative RT-PCR analysis showed that HF diet increases both CEACAM1 short (S) and long (L) isoforms in Pten mice leading to an S:L of 3.4 to 1. Because the tumor suppression activity of CEACAM1-L is regulated by a balanced S:L ratio, it is possible that this shift in S:L ratio by HF synergizes with Pten loss to cause a more progressive neoplastic form as compared to Pten mice on regular diet. The mechanism of this synergy between S:L imbalances and Pten loss is unclear. It could be related to (A) increased angiogenesis from endothelial CEACAM1, or (B) a dominant-negative effect on tumor suppression by the higher relative content of the short isoform in epithelial cells. Both possibilities warrant further studies. Taken together, this study suggests that lack of CEACAM1 activity potentiates neoplastic progression caused by Pten haploinsufficiency.
590 $a School code: 0232.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 $a The University of Toledo. $3 1023352
773 0 $t Dissertation Abstracts International $g 71-06B.
790 1 0 $a Najjar, Sonia M., $e advisor
790 $a 0232
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407732