美國研究人員18日報告說,，他們通過在實驗室模擬卵巢癌形成過程發(fā)現，卵巢癌可能始自輸卵管,，而非卵巢,。
美國達納－法伯癌癥研究所研究人員在新一期美國《國家科學院學報》上報告說，他們在一些攜帶卵巢癌基因的女性輸卵管組織中發(fā)現了“可能發(fā)展為嚴重癌癥的細胞”,，因此他們決定在實驗室內模擬卵巢癌形成過程,。
輸卵管是從女性卵巢連通至陰道的管道，包括中輸卵管和側輸卵管,，卵子經此管道排出,。研究人員提取一些輸卵管細胞并改變它們的基因片段，使其能夠像癌細胞那樣分裂,。實驗顯示,，和真正的癌細胞一樣，這些“人造”癌細胞可以迅速增殖,，并離開原發(fā)組織,，在其他組織內生長。如果把這些“人造”癌細胞植入動物體內,，它們能夠催生在結構,、行為和基因構成上與人類嚴重卵巢癌極其類似的腫瘤。
報告作者之一龍尼·德拉普金說,，這一研究表明卵巢癌可能來自輸卵管細胞,，它將有助于尋找新的卵巢癌生物標記物，為今后的卵巢癌治療提供了新的思路,。
卵巢癌是女性面臨的第5大癌癥,。據統(tǒng)計,，全球每年新增大約20萬卵巢癌患者，并有11．5萬患者死亡,。（生物谷Bioon.com）
生物谷推薦原文出處：
Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1017300108
Modeling high-grade serous ovarian carcinogenesis from the fallopian tube
Alison M. Karsta, Keren Levanona,1, and Ronny Drapkina,b,2
Abstract
High-grade serous ovarian carcinoma (HGSOC) is a lethal disease for which improved screening and treatment strategies are urgently needed. Progress in these areas is impeded by our poor understanding of HGSOC pathogenesis. Most ovarian cancer research is based on the hypothesis that HGSOC arises from ovarian surface epithelial cells. However, recent studies suggest that >50% of high-grade serous carcinomas involving the ovary likely arise from fallopian tube epithelium. Therefore, limiting HGSOC research to modeling based on ovarian surface epithelium alone is inadequate. To address the need for a fallopian tube–based model of HGSOC, we have developed a system for studying human fallopian tube secretory epithelial cell (FTSEC) transformation. Our model is based on (i) immortalization of FTSECs isolated from primary samples of normal, nondiseased human fallopian tubes, (ii) transformation of FTSECs with defined genetic elements, and (iii) xenograft-based tumorigenic assays. We use our model to show that FTSECs immortalized with human telomerase reverse transcriptase (hTERT) plus SV40 large T and small T antigens are transformed by either oncogenic Ras (H-RasV12) or c-Myc expression, leading to increased proliferation, clonogenicity, and anchorage-independent growth. Additionally, we demonstrate that FTSECs remain susceptible to c-Myc–mediated transformation in the absence of viral oncoproteins, by replacing SV40 large T and small T antigens with sh-p53, mutant CDK4 (CDK4R24C), and sh-PP2A-B56γ. Importantly, all transformed FTSECs gave rise to high-grade Müllerian carcinomas that were grossly, histologically, immunophenotypically, and genomically similar to human HGSOC. With this model, we will now be able to assess the transformative effects of specific genetic alterations on FTSECs in order to characterize their respective roles in HGSOC development.
