Abstract 3343: Anomalous expression of claudin 16 in ovarian cancer: Role of PKC, PI3K and estrogen
| العنوان: | Abstract 3343: Anomalous expression of claudin 16 in ovarian cancer: Role of PKC, PI3K and estrogen |
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| المؤلفون: | Klesia Pirola Madeira, Renata Dalmaschio Daltoé, Nayara G. Tessarollo, Marcela F. Paes, Leticia Batista Azevedo Rangel, Alice Laschuk Herlinger, Ian Victor Silva, Murilo F. Cerri |
| المصدر: | Cancer Research. 74:3343-3343 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, endocrine system diseases, Activator (genetics), Cancer, Biology, medicine.disease, Wortmannin, chemistry.chemical_compound, Endocrinology, Oncology, chemistry, Internal medicine, medicine, Cancer research, Claudin, Ovarian cancer, Cellular localization, Protein kinase C, PI3K/AKT/mTOR pathway |
| الوصف: | Background: We have demonstrated that 63% of primary epithelial ovarian cancer (EOC) anomalously overexpressed CLDN16 in the cell cytoplasm, regardless of tumor histological type or grade, thus suggesting that this is an early event in EOC development, and might serve as an EOC marker. The present work aimed to enlighten cellular mechanisms that modulate CLDN16 expression in EOC. Methods: PKA, PKC, and PI3K pathways affect CLDNs cellular localization and function, cancer development and progression. We investigated the effect of the pathways, and of intra-tumoral estrogen (0.5, 5, 50 and 500 nM), on CLDN16 expression in the serous and platinum-resistant EOC model, the OVCAR3 cell line. Immunofluorescence experiments were carried out to determine the cellular localization of CLDN16 in OVCAR3. CLDN16 expression was assessed by real-time RT-PCR, in the presence or absence of the pathway modulators cAMP (PKA activator, 10-6M), KT5720 (PKA inhibitor, 10-7M), PMA (PKC activator, 10-8M), and Wortmannin (WORT: PI3K activator, 10-7M). CLDN16 relative expression analyses followed the CT method of Pffalf, using the REST program (Version 2.0.13, 2009). Data, expressed as mean ± SE, were analyzed by Bonferroni and Dunnet multiple comparisons tests. Findings: OVCAR3 expressed CLDN16 exclusively in the cytoplasm compartment, resembling primary tumors, so being a reliable in vitro model to our expression study. While the PKA pathway did not affect CLDN16 expression in OVCAR3, the PKC pathway lead to an increase of the transcript by1.95-fold (PMA; p Conclusions: Our data strongly suggest that the expression of CLDN16 is stimulated by the PKC and PI3K, and intra-tumoral aromatase-produced estrogen in EOC. Whereas the anomalous cytoplasm overexpression of CLDN16 still puzzles us, we speculate that fragments of the molecule could be possibly secreted. If this is the case, screening for circulatory portions of the protein could serve as an EOC screening molecule, considering that it is overexpressed early in disease course. Despite the fact that more studies are necessary to elighten the mechanisms that control the expression and function of CLDN16 in EOC, our study opens a new avenue to overcome EOC dramatic epidemiological scenario, bringing hope to improve patients overall outcome and quality of life. Citation Format: Nayara G. Tessarollo, Marcela Paes, Murilo Cerri, Alice Herlinger, Klesia Madeira, Renata Daltoé, Ian Silva, Leticia Rangel. Anomalous expression of claudin 16 in ovarian cancer: Role of PKC, PI3K and estrogen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3343. doi:10.1158/1538-7445.AM2014-3343 |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2014-3343 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3032ae2be395f8dea910e435fd79cfe3 https://doi.org/10.1158/1538-7445.am2014-3343 |
| رقم الانضمام: | edsair.doi...........3032ae2be395f8dea910e435fd79cfe3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/1538-7445.am2014-3343 |