In normal breast and ductal carcinoma ill situ, myoepithelial cells surround the luminal cell population and form an interface with the basement membrane. In invasive breast cancers, the myoepithelial layer is lost. The aim of this project was to analyse the effect of normal breast myoepithelial cells on breast cancer cells and to investigate potential mechanisms of their modulatory activity. Using isolated primary myoepithelial cells and a myoepithelial cell line, 2-D and 3-D co-culture systems were used to analyse the effects of myoepithelial populations on breast tumour cell growth. cDNA microarray analysis identified pathways modulated by the myoepithelial populations, confirmed by real-time RT -PCR and Western blot analysis, and RNAi knockdown of target genes established a role for specific molecules in the myoepithelial modulation of tumour behaviour. Co-culture with the myoepithelial populations resulted in significant decrease in tumour cell proliferation and significant enhancement in apoptosis, in T47-D and MDA-MB- 468 breast cancer cell lines, in both 2-D and 3-D systems. Co-cultures with a normal luminal epithelial cell line showed no significant effect on tumour cell function, indicating that this growth suppressor effect was myoepithelial-specific. cDNA microarray analysis identified a number of potential tumour-suppressor genes that were up-regulated in T47-D cells grown in tlie presence of primary myoepithelial cells. These included the calcium-binding proteins SlOOA9 and SlOOA8, which showed an approximately 30-fold and 14-fold increase, confirmed by real-time RT -PCR and Western blotting.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:504548 |
| Date | January 2008 |
| Creators | Mulligan, Kellie Teresa |
| Publisher | Queen Mary, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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