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Use of regulatable mutantp53 and mut...

Keller, Gina M.

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Use of regulatable mutantp53 and mutant Kras to enhance prostate cancer models.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Use of regulatable mutantp53 and mutant Kras to enhance prostate cancer models./
作者:	Keller, Gina M.
面頁冊數:	114 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0704.
Contained By:	Dissertation Abstracts International67-02B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3207996
ISBN:	9780542570346

Use of regulatable mutantp53 and mutant Kras to enhance prostate cancer models.
Keller, Gina M.

Use of regulatable mutantp53 and mutant Kras to enhance prostate cancer models. - 114 p.

Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0704.

Thesis (Ph.D.)--Medical University of South Carolina, 2006.

Construction of a reproducible transgenic mouse model of prostate cancer which closely mimics human disease will not only help us study the early molecular mechanisms in prostate carcinogenesis but will also be valuable for testing novel gene therapeutic strategies. Previous work focused on targeting the restriction enzyme EcoRl (induces genomic instability) to the prostate using a hormonally regulated probasin (PB) short promoter. When prostates of PB-EcoRl mice were examined histologically at various time points, mild-to-severe hyperplasia, low and high grade prostatic intra-epithelial neoplasia (PIN) and well-differentiated adenocarcinoma, which correspond to early stages of the human condition, were observed [1]. However, these lesions developed in older mice, which limits our experimental treatment options. Therefore it was decided to develop mice with accelerated tumor formation earlier in life. To accomplish this transgenic mice (ARR2PB-rtTA-M2) were produced expressing the reverse tetracyclineresponsive transactivator fusion protein under the control of the modified, prostate specific, probasin promoter (ARR2PB). These mice were then crossed with transgenic mice in which either p53 (R270L) or Kras (G12D) mutants are present under the control of a Tet-operator (x7) regulated by the presence (ON) or absence (OFF) of doxycycline. In the presence of doxycycline (Tet-ON) and endogenous testosterone (puberty) the mutant gene (e.g. p53) is expressed. Multigenic (rtTA-M2 x p53R270L and/or KrasG12D) animals were crossed to the PB-Eco mice and given oral doxycycline starting at 4-8 weeks (post-puberty). Resultant multigenic animals are were analyzed at 0, 3, 6, and 9 months of doxycycline treatment. At 3 months of Dox treatment several bigenic animals showed areas with foci of stratification/hyperchromasia, intraluminal degenerated cells and enlarged vesicular nuclei in the dorsolateral and ventral prostate. After Dox treatment for 6 to 9 months the ventral prostate of different combinations of multigenic mice showed moderate to severe prostatic intraepithelial neoplasia (PIN), grades 1-4, as well as focal areas of invasion, and poorly differentiated adenocarcinoma.

ISBN: 9780542570346Subjects--Topical Terms:

1017719
Biology, Molecular.

Use of regulatable mutantp53 and mutant Kras to enhance prostate cancer models.
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