کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8478099 | 1550938 | 2010 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Chronology and complexities of ovarian tumorigenesis in FORKO mice: Age-dependent gene alterations and progressive dysregulation of Major Histocompatibility Complex (MHC) Class I and II profiles
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کلمات کلیدی
EOCIPAGDNFOSE - ORhuman leukocyte antigens - آنتی ژن های لکوستیک انسانیHLA - آنتیژن گلبول سفید انسانیOvarian surface epithelium - اپیتلیوم سطح تخمدانIngenuity Pathway Analysis - تجزیه و تحلیل راه IngenuityOvary - تخمدانTumors - تومورهاMicroarray - ریزآرایهAging - سالخوردگیOvarian cancer - سرطان تخمدانEpithelial ovarian cancer - سرطان تخمدان اپیتلیالTAP - ضربه زدنMHC - مجموعه سازگاری بافتی اصلیmajor histocompatibility complex - مجموعه سازگاری بافتی اصلیFSH - هورمون محرکه فولیکولی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Among gynecologic malignancies ovarian cancer is the deadliest and most difficult to detect at early stages. As ovarian tumors have long latency and are relatively more frequent in postmenopausal women, revealing chronological changes in model systems might help in the discovery of novel molecular targets and diagnostic biomarkers for disease detection and management. Follitropin receptor knockout (FORKO) mice with early and sustained sex steroid hormone disharmony develop various age-dependent ovarian abnormalities including increased incidence ovarian tumors in complete absence of ovulation. These mutants show various tumor cell types including those related to ovarian surface epithelium around 12-15 months of age. To explore why the FORKO mice develop ovarian tumors later in life, we assessed global gene expression changes during the pre-tumor period (at 8 months). Age-matched wild-type and FORKO mice were compared to gain a comprehensive view of genes that are misregulated, even before overt tumors appear in mutants. Applying a conservative 2-fold change to detect changes, our study identified 476 genes (338 upregulated and 138 downregulated) to be altered between 8-month-old FORKO and wild-type ovaries. Using Ingenuity Pathway Analysis (IPA), we found highly significant alterations in five functional networks in pre-tumor stage FORKO ovaries. Notably, the top network to change in 8-month-old FORKO ovaries was associated with functions implicated in immune system development and function. We selected 9 immune related genes that are reportedly altered in Epithelial Ovarian Cancer (EOC) in women and confirmed their expression and chronology of changes in FORKO ovaries before and after tumor development. Our data indicate that immune surveillance mechanisms are compromised with in a 4-month window of tumorigenic alterations. In addition, expression of previously unrecognized genes misregulated in the dysfunctional FORKO ovaries suggests mechanisms not yet appreciated to date. We propose that a better understanding of genes that change before overt tumors develop could provide useful insights into ovarian carcinogenesis and open the door to additional new targets for treating ovarian cancers.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 329, Issues 1â2, 25 November 2010, Pages 37-46
Journal: Molecular and Cellular Endocrinology - Volume 329, Issues 1â2, 25 November 2010, Pages 37-46
نویسندگان
J. Aravindakshan, X.L. Chen, M.R. Sairam,