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Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with con...

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Autores principales: Hua, Yuanyuan, Choi, Pui-Wah, Trachtenberg, Alexander J., Ng, Allen C., Kuo, Winston P., Ng, Shu-Kay, Dinulescu, Daniela M., Matzuk, Martin M., Berkowitz, Ross S., Ng, Shu-Wing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323216/
https://www.ncbi.nlm.nih.gov/pubmed/27602775
http://dx.doi.org/10.18632/oncotarget.11808
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author Hua, Yuanyuan
Choi, Pui-Wah
Trachtenberg, Alexander J.
Ng, Allen C.
Kuo, Winston P.
Ng, Shu-Kay
Dinulescu, Daniela M.
Matzuk, Martin M.
Berkowitz, Ross S.
Ng, Shu-Wing
author_facet Hua, Yuanyuan
Choi, Pui-Wah
Trachtenberg, Alexander J.
Ng, Allen C.
Kuo, Winston P.
Ng, Shu-Kay
Dinulescu, Daniela M.
Matzuk, Martin M.
Berkowitz, Ross S.
Ng, Shu-Wing
author_sort Hua, Yuanyuan
collection PubMed
description Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis.
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spelling pubmed-53232162017-03-23 Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma Hua, Yuanyuan Choi, Pui-Wah Trachtenberg, Alexander J. Ng, Allen C. Kuo, Winston P. Ng, Shu-Kay Dinulescu, Daniela M. Matzuk, Martin M. Berkowitz, Ross S. Ng, Shu-Wing Oncotarget Research Paper Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis. Impact Journals LLC 2016-09-01 /pmc/articles/PMC5323216/ /pubmed/27602775 http://dx.doi.org/10.18632/oncotarget.11808 Text en Copyright: © 2016 Hua et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Hua, Yuanyuan
Choi, Pui-Wah
Trachtenberg, Alexander J.
Ng, Allen C.
Kuo, Winston P.
Ng, Shu-Kay
Dinulescu, Daniela M.
Matzuk, Martin M.
Berkowitz, Ross S.
Ng, Shu-Wing
Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
title Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
title_full Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
title_fullStr Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
title_full_unstemmed Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
title_short Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
title_sort epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323216/
https://www.ncbi.nlm.nih.gov/pubmed/27602775
http://dx.doi.org/10.18632/oncotarget.11808
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