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Title: ErbB receptor regulation of growth in ovarian cancer
Author: Gilmour, Lynn M. R.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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Expression levels of the erbB receptors were measured in a panel of 16 ovarian cancer cell lines using Western blot analysis. While EGF receptor erbB2 and erbB3 were found in over 90% of cell lines, erbB4 receptor protein was only detected in half. Upon treatment with the ligands, 5/14 cell lines were growth stimulated by NRG1α, 7 by NRG1β and 8 by TGFα. In addition, one cell line was growth inhibited by treatment with both NRG1β or TGFα. A trend was observed in the magnitude of growth response to ligand and was of the order NRG1β TGFα NRG1α. Furthermore, a significant association between erbB2 receptor expression and magnitude of growth response to the NRG’s was detected and is consistent with erbB2 being the preferred hetero-dimerization partner. Expression of NRG mRNA was detected in the majority of both cell lines and tumours suggesting that this growth factor could potentially act in an autocrine manner to stimulate cell growth. Multiple erbB4 isoforms have previously been identified in other tissue types and demonstrated to possess differing functionalities. Investigation of the erbB4 receptor isoforms in a panel of 10 cell lines detected expression of the JM-a isoform (which is susceptible to proteolytic cleavage) in half, whilst expression of isoforms resistant to this type of cleavage was not detected. Expression of both the erbB4 receptor CT-a isoform (that is able to couple to PI3K and may promote cell survival) and the CT-b isoform (that is unable to bind PI3K) were detected in the same 5 cell lines. Similarly, expression of JM-a was detected in 18/24 human ovarian tumours whilst both CT-a and CT-b expression were detected in 22/24.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available