{"id":{"repo_id":"glasgow","oai_identifier":"oai:theses.gla.ac.uk:1099"},"canonical_url":"https://search.dev.ndltd.org/etd/glasgow/oai:theses.gla.ac.uk:1099","repository":{"repo_id":"glasgow","name":"University of Glasgow","base_url":"https://theses.gla.ac.uk/cgi/oai2"},"display":{"title":"A study of keratinocyte differentiation and adhesion in vitro","abstract":"In this study, I used the serum-free MCDB 153 culture system to investigate calcium-induced keratinocyte differentiation. Treating normal human keratinocytes with high extracellular calcium concentrations (1mM) increased the proportion of cells expressing differentiation-specific proteins. I showed that this was not caused by calcium-induced cell-cycle arrest, nor was it a consequence of stratification. However, the expression of differentiation-specific proteins was preceded by the formation of cadherin-mediated cell-cell adhesions. The likely importance of the cadherin-mediated adhesions in initiation the differentiation program was confirmed in two ways. Firstly, clustering cell-surface E-cadherin in low extracellular calcium using monoclonal antibodies increased the proportion of keratinocytes expressing differentiation-specific proteins. Secondly, suppressing the formation of cadherin-mediated cell-cell adhesions using synthetic peptide analogous to the cadherin recognition domain attenuated the calcium-induced expression of differentiation-specific proteins. These data are consistent with a role for the cadherin-mediated cell-cell adhesions in initiating the keratinocyte differentiation program in response to calcium in vitro. A second aspect of this project involved an investigation of the role played by the Src-family of protein tyrosine kinases at calcium-induced cadherin-mediated adherens junctions. The ubiquitously expressed members of this family, c-Src, Fyn and c-Yes were localised to the cadherin-mediated adhesions formed in response to high extracellular calcium. Treating adherent keratinocytes maintained in low extracellular calcium with a specific Src kinase inhibitor, PD162531, induced the assembly of cadherin-mediated cell-cell adhesions leading to the formation of contiguous groups of cells similar to those seen in response to high extracellular calcium. The data presented are consistent with a role for the Src kinases in regulating adherens junction turnover but do not exclude a role also in modulating aspects of differentiation.","abstract_html":"In this study, I used the serum-free MCDB 153 culture system to investigate calcium-induced keratinocyte differentiation. Treating normal human keratinocytes with high extracellular calcium concentrations (1mM) increased the proportion of cells expressing differentiation-specific proteins. I showed that this was not caused by calcium-induced cell-cycle arrest, nor was it a consequence of stratification. However, the expression of differentiation-specific proteins was preceded by the formation of cadherin-mediated cell-cell adhesions. The likely importance of the cadherin-mediated adhesions in initiation the differentiation program was confirmed in two ways. Firstly, clustering cell-surface E-cadherin in low extracellular calcium using monoclonal antibodies increased the proportion of keratinocytes expressing differentiation-specific proteins. Secondly, suppressing the formation of cadherin-mediated cell-cell adhesions using synthetic peptide analogous to the cadherin recognition domain attenuated the calcium-induced expression of differentiation-specific proteins. These data are consistent with a role for the cadherin-mediated cell-cell adhesions in initiating the keratinocyte differentiation program in response to calcium in vitro. A second aspect of this project involved an investigation of the role played by the Src-family of protein tyrosine kinases at calcium-induced cadherin-mediated adherens junctions. The ubiquitously expressed members of this family, c-Src, Fyn and c-Yes were localised to the cadherin-mediated adhesions formed in response to high extracellular calcium. Treating adherent keratinocytes maintained in low extracellular calcium with a specific Src kinase inhibitor, PD162531, induced the assembly of cadherin-mediated cell-cell adhesions leading to the formation of contiguous groups of cells similar to those seen in response to high extracellular calcium. The data presented are consistent with a role for the Src kinases in regulating adherens junction turnover but do not exclude a role also in modulating aspects of differentiation.","abstract_has_math":false,"creators":["Owens, Dewi W."],"institution":"University of Glasgow","degree_name":null,"degree_level":"PhD","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1997,"date_issued":"1997","date_published":"1997","updated_at":"2026-07-24T02:23:45Z","subjects":["RC0254 Neoplasms. Tumors. 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However, the expression of differentiation-specific proteins was preceded by the formation of cadherin-mediated cell-cell adhesions. The likely importance of the cadherin-mediated adhesions in initiation the differentiation program was confirmed in two ways. Firstly, clustering cell-surface E-cadherin in low extracellular calcium using monoclonal antibodies increased the proportion of keratinocytes expressing differentiation-specific proteins. Secondly, suppressing the formation of cadherin-mediated cell-cell adhesions using synthetic peptide analogous to the cadherin recognition domain attenuated the calcium-induced expression of differentiation-specific proteins. These data are consistent with a role for the cadherin-mediated cell-cell adhesions in initiating the keratinocyte differentiation program in response to calcium in vitro. A second aspect of this project involved an investigation of the role played by the Src-family of protein tyrosine kinases at calcium-induced cadherin-mediated adherens junctions. The ubiquitously expressed members of this family, c-Src, Fyn and c-Yes were localised to the cadherin-mediated adhesions formed in response to high extracellular calcium. Treating adherent keratinocytes maintained in low extracellular calcium with a specific Src kinase inhibitor, PD162531, induced the assembly of cadherin-mediated cell-cell adhesions leading to the formation of contiguous groups of cells similar to those seen in response to high extracellular calcium. The data presented are consistent with a role for the Src kinases in regulating adherens junction turnover but do not exclude a role also in modulating aspects of differentiation."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["A study of keratinocyte differentiation and adhesion in vitro"]}]}],"canonical_facts":{"dc:creator":["Owens, Dewi W."],"dc:date":["1997"],"dc:date.issued":["1997"],"dc:description.abstract":["In this study, I used the serum-free MCDB 153 culture system to investigate calcium-induced keratinocyte differentiation. Treating normal human keratinocytes with high extracellular calcium concentrations (1mM) increased the proportion of cells expressing differentiation-specific proteins. I showed that this was not caused by calcium-induced cell-cycle arrest, nor was it a consequence of stratification. However, the expression of differentiation-specific proteins was preceded by the formation of cadherin-mediated cell-cell adhesions. The likely importance of the cadherin-mediated adhesions in initiation the differentiation program was confirmed in two ways. Firstly, clustering cell-surface E-cadherin in low extracellular calcium using monoclonal antibodies increased the proportion of keratinocytes expressing differentiation-specific proteins. Secondly, suppressing the formation of cadherin-mediated cell-cell adhesions using synthetic peptide analogous to the cadherin recognition domain attenuated the calcium-induced expression of differentiation-specific proteins. These data are consistent with a role for the cadherin-mediated cell-cell adhesions in initiating the keratinocyte differentiation program in response to calcium in vitro. A second aspect of this project involved an investigation of the role played by the Src-family of protein tyrosine kinases at calcium-induced cadherin-mediated adherens junctions. The ubiquitously expressed members of this family, c-Src, Fyn and c-Yes were localised to the cadherin-mediated adhesions formed in response to high extracellular calcium. Treating adherent keratinocytes maintained in low extracellular calcium with a specific Src kinase inhibitor, PD162531, induced the assembly of cadherin-mediated cell-cell adhesions leading to the formation of contiguous groups of cells similar to those seen in response to high extracellular calcium. The data presented are consistent with a role for the Src kinases in regulating adherens junction turnover but do not exclude a role also in modulating aspects of differentiation."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://theses.gla.ac.uk/1099/1/1997owensphd.pdf"],"dc:language":["en"],"dc:publisher.institution":["University of Glasgow"],"dc:relation.isreferencedby":["https://theses.gla.ac.uk/1099/"],"dc:relation.isreferencedby.uri":["https://gla.on.worldcat.org/oclc/53624357"],"dc:subject":["RC0254 Neoplasms. Tumors. Oncology (including Cancer)"],"dc:title":["A study of keratinocyte differentiation and adhesion in vitro"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["PhD"]},"updated_at":"2026-07-24T02:23:45Z"}