Kras和 p53在子宮內膜異位相關卵巢肉瘤癌老鼠中所扮演的角色

Role of Kras and p53 in endometriosis associated ovary carcinosarcoma in the mouse model

林筱芸(Hsiao-Yun Lin)

指導教授 ： 蔡英美

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2015年)

摘要

卵巢癌在2014年國人十大死因中，女性癌症死亡中排名為第8名的癌症，在婦科癌症中死亡率也位居於首位，它是一個具有複雜的臨床症狀、診斷和治療的疾病，因為卵巢癌早期發現困難，並且缺乏明顯的癌前病變，所以有很高的死亡率，要降低卵巢癌的致命威脅、尋找及研究可能的癌前病變，是非常重要的議題，近來有學者注意到內膜異位症和卵巢癌症有其相關性，因而推測子宮內膜異位症很有可能是卵巢癌前病變之一，機制尚不完全清楚。因此我們由基因變異層面來研究並發現KrasG12D和p53loxP/loxP會引起卵巢上皮細胞的增生與子宮內膜腺體形態之癌前病變，並利用組織型態學和免疫組織染色判斷Kras 與p53 兩個突變可導致卵巢肉瘤癌形成且只需4週的疾病潛伏期。另外，我們利用卵巢癌細胞株MCAS(KrasG12D/p53MT)和PA-1(KrasWT/p53WT) 驗證動物實驗，實驗結果發現MCAS有較強的細胞增生、爬行及侵襲能力。總結來說，這是一個新型內膜異位症相關之卵巢肉瘤癌老鼠模型，期許對於未來診斷此疾病及臨床治療藥物的開發有所貢獻。

關鍵字

Kras ； p53 ； 卵巢表面上皮 ； 老鼠模型 ； 體內 ； 卵巢肉瘤癌

並列摘要

Ovarian cancer is the eighth among the top ten cancer of death and the most lethal form of gynecologic malignancy according to the Taiwan health bureau report in 2014. Recently the researchers have found the association of endometriosis and ovarian cancer, and assume that endometriosis to be one of the precursor diseases. This inspires us to study on the genetic mutation animal models of endometriosis malignant transformation. We established the transgenic mouse model of KrasG12D /p53loxP/loxP and found that Kras mutation and p53 deletion within the ovarian surface epithelium gives rise to ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic ovarian cancer with complete penetrance and a disease latency of only 4 weeks. In addition, we confirmed the animal model through ovarian cancer cell lines MCAS(KrasG12D/p53MT) and PA-1 (KrasWT/p53WT) as well as the results showed that MCAS has strong proliferation, migration and invasion compare to PA-1. The ovarian cancer model described in thesis recapitulates the specific tumor histomorphology and the probable mechanism of endometriosis malignant transformation.

並列關鍵字

Kras ； p53 ； ovarian surface epithelium ； mouse model ； in-vivo ； ovary cracinosarcoma

參考文獻

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