Breast biology
Led by Dr Robert Clarke
The goal of the group's research is to understand the hierarchical relationship between cells in breast epithelium in order to gain an insight into the processes that underlie cancer initiation in this tissue.
Research aims
The primary aim is to characterise and to understand the regulation of mammary epithelial stem cells since these are likely to be the targets of cancer-initiating events, and may be the underlying tumourigenic cells in breast cancers. The secondary aim is to understand how steroid hormones such as oestrogen regulate this hierarchy since both normal and tumour development is hormone dependent.
Since mammary development and breast tumourigenesis are promoted by the ovarian steroids oestrogen and progesterone, we are concerned with the mechanisms by which these hormones control stem cells and proliferative progeny in normal breast tissue. The group was the first to demonstrate that steroid receptors are limited to a non-proliferative sub-population, often found adjacent to dividing cells (figure 1), and that they may therefore control proliferation via paracrine factors (Clarke et al., 1997).
Figure 1:
Section of normal human breast epithelium stained using a dual-label immunofluorescent technique to show the presence of oestrogen receptor-alpha containing cells (red) in relation to proliferation-competent cells that express the replication licencing protein MCM2 (green).
Mini-chromosome maintenance (MCM) protein expression is required for all phases of the cell cycle and in non-proliferating cells that are competent to divide.
Development of the mammary gland involves the formation of collecting ducts and lobules, both of which are bilayered epithelia made up of contractile myo-epithelial and milk-producing luminal cells. The group has recently developed new methods for the isolation and characterisation of putative breast epithelial stem cells that give rise to these two cell types (Clarke et al., 2005). One current interest is which of the Notch, Hedgehog, Wnt, TGFbeta, EGF pathways and other relevant (eg Prl, GH and ovarian hormones) signalling-pathways regulate stem cell self-renewal. We are also exploiting gene-expression arrays and methods for functional genomics to identify novel pathways that participate in stem-cell regulation.
Staff members
| Name | Job title | Email adress |
|---|---|---|
| Robert Clarke | CR-UK Research Fellow, Honorary Lecturer in Cancer Cell Biology and Breast Biology Group Leader | robert.clarke@manchester.ac.uk |
| Gillian Farnie | Research Associate | gfarnie@manchester.ac.uk |
| Rebecca Lamb | Research Associate | rebecca.lamb@manchester.ac.uk |
| Andrew Sims | Postdoctoral Research Associate | Andrew.H.Sims@manchester.ac.uk |
| Kath Spence | Scientific Officer | |
| Rognald Blance | Scientific Officer | |
| Noxa Nguyen-Huu | Postgraduate Student | |
| Hannah Harrison | Postgraduate Student |
Further information
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