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Cancers, Vol. 13, Pages 3174: Establishment of a Novel In Vitro Model of Endometriosis with Oncogenic KRAS and PIK3CA Mutations for Understanding the Underlying Biology and Molecular Pathogenesis
Tohru Kiyono Satoru Kyo Endometriosis-harboring cancer-associated somatic mutations of PIK3CA and KRAS provides new opportunities for studying the multistep processes responsible for the functional and molecular changes in this disease. We aimed to establish a novel in vitro endometriosis model to clarify the functional behavior and molecular pathogenesis of this disorder. Immortalized HMOsisEC10 human ovarian endometriotic epithelial cell line was used in which KRAS and PIK3CA mutations were introduced. Migration, invasion, proliferation, and microarray analyses were performed using KRAS and PIK3CA mutant cell lines...
Source: Cancers - June 25, 2021 Category: Cancer & Oncology Authors: Mohammad Mahmud Hossain Kentaro Nakayama Kamrunnahar Shanta Sultana Razia Masako Ishikawa Tomoka Ishibashi Hitomi Yamashita Seiya Sato Kouji Iida Kosuke Kanno Noriyoshi Ishikawa Tohru Kiyono Satoru Kyo Tags: Article Source Type: research

Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma
STUDY QUESTION Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma? SUMMARY ANSWER Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma. WHAT IS KNOWN ALREADY Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype. STUDY DESIGN, SIZE, DURATION Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of...
Source: Human Reproduction - March 15, 2016 Category: Reproduction Medicine Authors: Zhan, H., Ma, J., Ruan, F., Bedaiwy, M. A., Peng, B., Wu, R., Lin, J. Tags: Gynaecology Source Type: research

Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice.
Abstract Women with endometriosis can suffer from decreased fecundity or complete infertility via abnormal oocyte function or impaired placental-uterine interactions required for normal pregnancy establishment and maintenance. Although AT-rich interactive domain 1A (SWI-like) (ARID1A) is a putative tumor suppressor in human endometrial cancers and endometriosis-associated ovarian cancers, little is known about its role in normal uterine function. To study the potential function of ARID1A in the female reproductive tract, we generated mice with a conditional knockout of Arid1a using anti-Müllerian hormone receptor...
Source: Biology of Reproduction - March 9, 2016 Category: Reproduction Medicine Authors: Wang X, Khatri S, Broaddus R, Wang Z, Hawkins SM Tags: Biol Reprod Source Type: research

Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas.
Abstract The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated. Inhibition of autophagy by chloroquin...
Source: International Journal of Oncology - October 6, 2015 Category: Cancer & Oncology Authors: Katagiri H, Nakayama K, Razia S, Nakamura K, Sato E, Ishibashi T, Ishikawa M, Iida K, Ishikawa N, Otsuki Y, Nakayama S, Kyo S Tags: Int J Oncol Source Type: research

BAD-mediated apoptotic pathway is associated with human cancer development.
Abstract The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive ...
Source: International Journal of Molecular Medicine - February 5, 2015 Category: Molecular Biology Authors: Stickles XB, Marchion DC, Bicaku E, Al Sawah E, Abbasi F, Xiong Y, Bou Zgheib N, Boac BM, Orr BC, Judson PL, Berry A, Hakam A, Wenham RM, Apte SM, Berglund AE, Lancaster JM Tags: Int J Mol Med Source Type: research

151pd * arid1a role in cell cycle regulation and proliferation in mouse and human gynaecological tissues reveals potential therapeutic targets
Conclusions: A core ARID1A-driven transcriptional programme, conserved accross normal tissues and species appears to exist, centred around regulation of genes involved in the G2/M checkpoint. ARID1A loss promotes proliferation in normal tissues, providing important clues as to the mechanisms of ARID1A-driven carcinogenesis. Mitotic kinases emerge as potential therapeutic targets in ARID1A mutant tumours, an observation that is not evident from studies in cancer cell lines.Disclosure: All authors have declared no conflicts of interest.
Source: Annals of Oncology - September 24, 2014 Category: Cancer & Oncology Authors: Gounaris, I., Brenton, J. Tags: basic science Source Type: research

A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation
Background: Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC. Methods: Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33...
Source: BMC Cancer - February 22, 2014 Category: Cancer & Oncology Authors: Kimberly WiegandBryan HennessySamuel LeungYemin WangZhenlin JuMollianne McGahrenSteve KallogerSarah FinlaysonKatherine Stemke-HaleYiling LuFan ZhangMichael AnglesioBlake GilksGordon MillsDavid HuntsmanMark Carey Source Type: research