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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
cAMP response element-binding (CREB) signalling and ovarian surface epithelial cell survival
O Gubbay1, M T Rae, A S McNeilly
1Division of Reproductive and Developmental Sciences, Queen's Medical Research Institute, Centre for Reproductive Biology, University of Edinburgh, 47 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4TJ, UK.
The Journal of Endocrinology
|October 27, 2006
Summary
CREB/ATF signaling promotes ovarian surface epithelium cell survival and is altered in ovarian cancer cells. This pathway
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- CREB (cAMP response-element binding) transcription factors are crucial for cell survival signaling.
- Ovarian cancer often originates from the ovarian surface epithelium (OSE), potentially linked to inflammation-induced repair.
- The role of CREB signaling in OSE cell survival and its alteration in ovarian cancer remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of CREB/ATF signaling in ovarian surface epithelium (OSE) cell survival.
- To determine if CREB signaling is altered in human ovarian cancer cell lines.
Main Methods:
- Immunohistochemistry to detect phospho-CREB/ATF in ovine OSE cells.
- Primary sheep OSE cell culture treated with LH and FSH, measuring cAMP and apoptosis.
- Adenoviral expression of CRE-luciferase and CREB mutants (S133A, WT) in OSE cells.
- Apoptosis assays in normal human OSE cells and ovarian cancer cell lines expressing mutant CREB.
Main Results:
- Phospho-CREB/ATF was abundant in ovine OSE cells near pre-ovulatory follicles.
- LH stimulation reduced apoptosis and increased cAMP in sheep OSE cells.
- LH and FSH induced CRE-directed transcription in OSE cells.
- Expression of a non-phosphorylatable CREB mutant (Ad CREB(S133A)) significantly increased apoptosis in normal human OSE cells but not in ovarian cancer cell lines.
Conclusions:
- CREB/ATF signaling is vital for maintaining OSE cell survival in vitro.
- This signaling pathway is dysregulated in human ovarian cancer cell lines.
- Targeting CREB/ATF signaling may offer therapeutic strategies for ovarian cancer.
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