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Title: Expression of the c-fgr proto-oncogene in monoblastoid cells
Author: Faulkner, Lee
ISNI:       0000 0001 3458 3214
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1995
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Expression of the c-fgr proto-oncogene is normally restricted to differentiated cells which belong to the myeloid lineage and is also found in some B cell lines. The aim of this thesis was to investigate the role of c-fgr in myeloid cells using the monoblastoid U937 cell line as a model system. Expression of c-fgr was increased when U937 cells were induced to differentiate by phorbol 12-myristate 13-acetate [PMA], dihydroxycholecalciferol [DHCC], tumour necrosis factor alpha [TNFα] or retinoic acid. The level of c-fgr mRNA or p55c-fgr detected in these cells varied depending on the agent used and did not correlate with the degree of growth inhibition induced by the agent. FCγR crosslinking in U937 cells treated with PMA or DHCC resulted in the modulation of p55c-fgr and in tyrosine phosphorylation of cellular proteins. Both protein kinase C and protein kinase A [PKA] were implicated as second messengers in the induction of c-fgr mRNA by PMA, and PKA was implicated as a second messenger in the induction of c-fgr mRNA by TNFα. Tyrosine kinases were not involved in the regulation of c-fgr mRNA by either PMA or TNFα. The level of c-fgr mRNA detected in three Burkitt's lymphoma cell lines was increased by retinoic acid, but this also did not correlate with growth inhibition induced by this agent. To examine the role of c-fgr in more detail, the gene was inserted into an inducible expression vector and stably transfected U937 clones were isolated. Hyper-expression of the transfected c-fgr gene did not affect cell growth, responses to PMA, DHCC, TNFα or retinoic acid, adhesion to fibronectin, phagocytosis or tyrosine phosphorylation of cellular proteins, but did induce increased expression of 52U, a cytoplasmic antigen and ICAM-2, increased expression of ICAM-1 in the presence of DHCC and decreased expression of five myeloid antigens and ICAM-3.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Myeloid cells