Stem cell divisions controlled by the proto-oncogene BMI-1.

Divisions of somatic stem cells are required for the maintenance and regeneration of normal tissues, while divisions of cancerous stem cells likely underlie the existence of certain malignant diseases. Studies of recent years suggest that molecular mechanisms governing stem cell self-renewal can be subverted in tumorigenesis to maintain cancerous growth. This is exemplified by the proto-oncogene BMI-1 that is involved in the maintenance of somatic stem cells and in carcinogenesis within the same tissues. BMI-1 interferes with the central cellular tumor suppressor pathways linked to retinoblastoma protein (Rb) and p53. These signaling pathways control the cell cycle, cell differentiation, cellular senescence and cell death. While the roles of the pathways associated with Rb and p53 in cancer are broadly established, further elucidation thereof in stem cells might have implications in cancer research, stem cell biology and regenerative medicine.