자료유형  

 학위논문

Control Number  

0016935169

International Standard Book Number  

9798380072076

Dewey Decimal Classification Number  

612

Main Entry-Personal Name  

Fang, Xin.

Publication, Distribution, etc. (Imprint  

[S.l.] : Texas A&M University., 2022

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2022

Physical Description  

1 online resource(157 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-02, Section: B.

General Note  

Advisor: Li, Qinglei.

Dissertation Note  

Thesis (Ph.D.)--Texas A&M University, 2022.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Reproductive development and tumorigenesis are the two main topics in reproductive research. Enhancer of zeste (EZH2), a core component of Polycomb Repressive Complexes 2, possesses histone methyltransferase activity that catalyzes the trimethylation of lysine 27 of histone H3. It has been shown that EZH2 is involved in epithelial to mesenchymal transition (EMT), a key event in development and carcinogenesis. However, the role of EZH2 in the uterus and endometrial cancer remains poorly defined. In Aim 1, we generated a mouse model harboring conditional deletion of Ezh2 in the uterus. The uterine epithelium became stratified and further developed into endometrial hyperplasia in this mouse model. Fertility defects accompanied by altered uterine growth and function were also found in the Ezh2 conditional knockout (Ezh2 cKO) mice. Findings suggest EZH2 protects epithelial integrity partially by inhibiting the differentiation of basal-like cells and preventing epithelial stratification. To study the role of Ezh2 in endometrial cancer development, we generate a mouse model with double deletion of both Ezh2 and Pten in Aim 2. Compared to Ptend/d mice, reduced tumor burdens were observed in the Ptend/d; Ezh2d/d mice. However, the deletion of Ezh2 induced altered immune response, enhanced inflammation, and exacerbated epithelial stratification, leading to unfavorable disease outcomes. These results suggest EZH2 plays dual roles in endometrial cancer development. Aim 3 of the dissertation was to study mechanism underlying the development of testicular granulosa cell tumors (TGCTs), a type of rare tumor in the testis. A mouse model with constitutively activative transforming growth factor beta receptor 1 (TGFBR1) in the testis was generated. The development of sex cord-stromal tumor, resembling TGCT, led to overproliferation in Sertoli cells and defective spermatogenesis. The testicular tumors were identified as TGCTs for the positive staining of granulosa cell markers including INHA, FOXO1, and FOXL2 essential for ovarian granulosa cell differentiation and functions. Thus, Aim 3 uncovered an oncogenic role of TGFβ signaling in the testis. In summary, these studies have identified mechanisms of reproductive development and tumorigenesis and will potentially guide the development of targeted therapy for pregnancy failure and tumors in the reproductive system.

Subject Added Entry-Topical Term  

Physiology.

Subject Added Entry-Topical Term  

Animal sciences.

Subject Added Entry-Topical Term  

Genetics.

Subject Added Entry-Topical Term  

Oncology.

Index Term-Uncontrolled  

Mouse model

Index Term-Uncontrolled  

EZH2

Index Term-Uncontrolled  

TGFβ signaling

Index Term-Uncontrolled  

Reproductive tract

Index Term-Uncontrolled  

Cell tumors

Added Entry-Corporate Name  

Texas A&M University Veterinary Integrative Biosciences

Host Item Entry  

Dissertations Abstracts International. 85-02B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643878