Self-renewing divisions of normal and cancerous stem cells are responsible for 
the initiation and maintenance of normal and certain cancerous tissues, 
respectively. Recent findings suggest that tumor surveillance mechanisms can 
reduce regenerative capacity and frequency of normal stem cells, thereby 
contributing to tissue aging. Signaling pathways promoting self-renewal of stem 
cells can also drive proliferation in cancer. The BMI-1 proto-oncogene is 
required for the maintenance of tissue-specific stem cells and is involved in 
carcinogenesis within the same tissues. BMI-1 promotes self-renewal of stem 
cells largely by interfering with two central cellular tumor suppressor 
pathways, p16(Ink4a)/retinoblastoma protein (Rb) and ARF/p53, whose disruption 
is a hallmark of cancer. Nucleolin, an Rb-associated protein, is abundant in 
proliferating cancerous cells and likely contributes to the maintenance of human 
CD34-positive stem/progenitor cells of hematopoiesis. Elucidation of the 
involvement of proto-oncogenes and tumor suppressors in the maintenance of stem 
cells might have therapeutic implications.