Academic Journal
Endometrial cancer cells exhibit high expression of p110β and its selective inhibition induces variable responses on PI3K signaling, cell survival and proliferation
| العنوان: | Endometrial cancer cells exhibit high expression of p110β and its selective inhibition induces variable responses on PI3K signaling, cell survival and proliferation |
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| المؤلفون: | Karlsson, Thomas, Krakstad, Camilla, Tangen, Ingvild Løberg, Høivik, Erling Andre, Pollock, Pamela M., Salvesen, Helga, Lewis, Aurelia Eva |
| المصدر: | OncoTarget |
| بيانات النشر: | Impact Journals |
| سنة النشر: | 2018 |
| المجموعة: | University of Bergen: Bergen Open Research Archive (BORA-UiB) |
| الوصف: | PTEN loss and constitutive activation of the class I phosphoinositide 3-kinase (PI3K) pathway are key drivers of endometrial tumorigenesis. In some cancer types, PTEN-deficient tumors are reliant on class I PI3K p110β (encoded by PIK3CB) activity but little is known about this contribution in endometrial tumorigenesis. In this study, we find that p110β is overexpressed in a panel of 7 endometrial cancer cell lines compared to non-transformed cells. Furthermore, in 234 clinically annotated patient samples, PIK3CB mRNA levels increase significantly in the early phase of tumorigenesis from precursors to low grade primary malignant lesions whereas PIK3CA levels are higher in non-endometrioid compared to endometrioid primary tumors. While high levels of either PIK3CA or PIK3CB associate with poor prognosis, only elevated PIK3CB mRNA levels correlate with a high cell cycle signature score in clinical samples. In cancer cell lines, p110α inhibition reduces cell viability by inducing cell death in PIK3CA mutant cells while p110β inhibition delayed proliferation in PTEN-deficient cells, but not in WT cells. Taken together, our findings suggest that PIK3CB/p110β contributes to some of the pleiotropic functions of PI3K in endometrial cancer, particularly in the early steps by contributing to cell proliferation. ; publishedVersion |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1949-2553 |
| Relation: | urn:issn:1949-2553; https://hdl.handle.net/1956/17657; https://doi.org/10.18632/oncotarget.13989; cristin:1428481 |
| DOI: | 10.18632/oncotarget.13989 |
| الاتاحة: | https://hdl.handle.net/1956/17657 https://doi.org/10.18632/oncotarget.13989 |
| Rights: | Attribution CC BY ; http://creativecommons.org/licenses/by/3.0/ ; Copyright 2017 The Author(s) |
| رقم الانضمام: | edsbas.827C55A5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19492553 |
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| DOI: | 10.18632/oncotarget.13989 |