A stem cell can divide to form either additional stem cells that are identical to itself (self-renewal), or more specialised mature cells that make up the various tissues of the body (differentiation). In early 2006, stem cells were identified in the mouse mammary gland. This was an important discovery that also implicated mammary epithelial stem cells in the development of breast cancer. This is partly because stem cells are relatively long-lived compared to other cells, and thus have a greater opportunity to accumulate mutations that cause cancer. Also, stem cells have a capacity for self-renewal and unlimited replication, properties that are also exhibited by cancer cells. It would theoretically be easier for a stem cell to lose its tightly regulated control on these processes and become cancerous than it would be for a differentiated cell to reacquire these stem cell-like properties.
Aims and Relevance
The idea that stem cells are involved in cancer has significant implications for cancer therapy, particularly with regards to drug resistance. Stem cells often express drug-resistance proteins and high levels of proteins that block apoptosis (cell death). If cancer stem cells can be forced to differentiate, they would lose this drug resistance and become more sensitive to chemotherapy. Thoroughly characterizing normal mammary stem cells will allow us to determine what processes encourage differentiation, with the hope of triggering this pathway in cancer stem cells. Additionally, basic information regarding the factors that govern the growth and differentiation of normal stem cells will allow us to determine what drives malignant transformation and provide clues into how to prevent cancer initiation.
My laboratory is using whole-genome screening techniques to identify genes that are involved in the proliferation of epithelial stem cells, and in their differentiation into other cell types. We are also investigating how proteins interact during these processes, focusing initially on several proteins that are known to play a role in breast cancer. Other lab members are also working on methods that will improve the efficiency of mouse mammary stem cell isolation. Success in this endeavour will enable new experimental approaches and decrease the number of animals needed in our research.
Recent related papers from the Aparicio Laboratory
- Holland D, Burleigh A, Git A, Goldgraben MA, Perez-Mancera PA, Chin SF, Hurtado A, Bruna A, Ali R, Greenwood W, Dunning MJ, Samarajiwa S, Menon S, Rueda OM, Lynch AG, McKinney S, Ellis IO, Eaves CJ, Carroll JS, Curtis C, Aparicio S, Caldas C. ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium. EMBO Mol Med 2011 3:1–14
- Eirew P, Stingl J, Raouf A, Turashvili G, Aparicio S, Emerman J & Eaves CJ. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat Med 2008: 14(12):1384-9.
- Raouf A, Zhao Y, To K, Stingl J, Delaney A, Iscove N, Jones S, Emerman J, Aparicio S, Marra M & Eaves C. Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell 2008: 3(1):109-18.