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You searched for id:"oai:escholar.manchester.ac.uk:uk-ac-man-scw-320501". One record found.

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University of Manchester

1. Kaabi, Hassan Hamed. The epigenetic effects of exogenous E-cadherin inhibition in MCF7 epithelial cells.

Degree: 2019, University of Manchester

The epithelial cadherin (E-cadherin) mediates lateral adhesion in epithelial tissues and thus organises the epithelial architecture. E-cadherin functions, however, are not limited to cell adhesion. Recent work in our lab using microarray analysis has shown that inhibition of E-cadherin in the human breast cancer cell line MCF7 was sufficient for inducing changes in transcript levels of genes associated with multiple biological processes. Similarities at the transcript level were described between E-cadherin-inhibited MCF7 cells and naïve human embryonic stem cells. EP300, a transcriptional co-activator and an acetyltransferase, was identified as a core modulator driving the transcriptome in E-cadherin-inhibited MCF7 cells, using a network modelling tool. However, the role of EP300 and the epigenetic mechanism underlying the changes observed remain to be elucidated. In the present study, the E-cadherin neutralising antibody SHE78.7 (nAb) has been used to assess how exogenous inhibition of E cadherin affects the epigenome. The genome-wide binding signatures for EP300 and the histone modification H3K27ac, and DNA methylation have been investigated using chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) and reduced representation bisulfite sequencing (RRBS) techniques, respectively. Genome wide EP300 and H3K27ac signatures and CpG methylation were altered upon inhibition of E-cadherin protein function. The putative genes associated with the alteration were related to multiple biological processes among which EMT and cancer stem cell, dedifferentiation phenotypes were identified. Normal human primary gingival keratinocytes (HPGKs) were used to test transcript changes observed in MCF7 cells. The results revealed to some extent a similar trend to MCF7 cells and highlighting an increase in EMT and pluripotency markers, and the differentiation marker SUZ12 upon E-cadherin inhibition. Altogether, these results show that exogenous inhibition of E-cadherin in MCF7 cells is associated with epigenetic alterations as demonstrated by differential genomic binding for EP300 and H3K27ac marks along with differential CpG methylation. Also, preliminary findings indicate a similar behaviour between cancer and normal epithelial cells following E-cadherin inhibition. Advisors/Committee Members: Doig, Andrew.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Kaabi, H. H. (2019). The epigenetic effects of exogenous E-cadherin inhibition in MCF7 epithelial cells. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:320501

Chicago Manual of Style (16th Edition):

Kaabi, Hassan Hamed. “The epigenetic effects of exogenous E-cadherin inhibition in MCF7 epithelial cells.” 2019. Doctoral Dissertation, University of Manchester. Accessed September 21, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:320501.

MLA Handbook (7th Edition):

Kaabi, Hassan Hamed. “The epigenetic effects of exogenous E-cadherin inhibition in MCF7 epithelial cells.” 2019. Web. 21 Sep 2019.

Vancouver:

Kaabi HH. The epigenetic effects of exogenous E-cadherin inhibition in MCF7 epithelial cells. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2019 Sep 21]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:320501.

Council of Science Editors:

Kaabi HH. The epigenetic effects of exogenous E-cadherin inhibition in MCF7 epithelial cells. [Doctoral Dissertation]. University of Manchester; 2019. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:320501

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