Speaker: Özlen Konu, Bilkent University
Title: Deciphering the role of cholinergic signals in breast and hepatocellular cancers
Date/Time: December 4, 2019 / 13.40-14.30
Place: FENS G032
Abstract: Nicotinic acetylcholine receptors (nAChRs), which occur as homo- or heteromeric complexes on the plasma membrane, play significant roles in determining the cellular fate. Acetylcholine, the natural ligand of nAChRs that is metabolized by acetylcholinesterase (ACHE) enzyme, modulates the action of these cholinergic receptors in both neuronal and non-neuronal cells, along with nicotine, the addictive component of tobacco. Human cancer cell proliferation and apoptosis, primarily for the lung cancer, have already been shown to be modulated by divergent cholinergic signals. However, it is still unclear whether/which cholinergic signals have roles in the development of breast and hepatocellular cancers. In recent years, research in my lab has focused on effects of cholinergic receptor nicotinic alpha 5 subunit (CHRNA5) expression on cell proliferation and drug sensitivity of breast cancer cells using RNAi and bioinformatics approaches. Our findings implicated the elevated expression of CHRNA5, a well-known biomarker in lung cancer, in the development of drug resistance in breast cancer. We also developed an in vivo zebrafish xenograft model to test whether microenvironment could contribute to tumor development using liver cancer cell lines. Zebrafish ache null mutant embryos and healthy siblings, micro-injected with liver cancer cells, were screened using microscopic and DNA-based xenograft assays. We observed larger tumors in ache mutant than in wildtype larvae suggesting that excess acetylcholine can modulate directly or indirectly the size of liver tumors. Our findings overall implicate selected cholinergic signaling components in the development and progression of breast and liver cancers and warrant further studies.
BIO: Dr. Ozlen Konu graduated from Middle East Technical University with a B.S. degree in Biological Sciences. Dr. Konu pursued her graduate studies at Texas Tech University, receiving her M.S. and Ph.D. degrees respectively in systems biology modeling and developmental biology. She was a postdoctoral research fellow at the University of Tennessee at Memphis, USA, during 2000-2002. Since September 2002, she is a faculty member at the Department of Molecular Biology and Genetics at Bilkent University. Her research interests include gene expression data analysis and meta-analysis with respect to cholinergic and mineralocorticoid receptor signaling in cancer, and comparative expression profiling using the zebrafish model.
Contact: Öznur Taştan