Mammary stem cells, self-renewal pathways, and carcinogenesis.
The mammary gland epithelial components are thought to arise from stem cells that undergo both self-renewal and differentiation. Self-renewal has been shown to be regulated by the Hedgehog, Notch, and Wnt pathways and the transcription factor B lymphoma Mo-MLV insertion region 1 (Bmi-1). We review data about the existence of stem cells in the mammary gland and the pathways regulating the self-renewal of these cells. We present evidence that deregulation of the self-renewal in stem cells/progenitors might be a key event in mammary carcinogenesis. If 'tumor stem cells' are inherently resistant to current therapies, targeting stem cell self-renewal pathways might provide a novel approach for breast cancer treatment.
Liu
Suling
S
Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. sulingl@med.umich.edu
Dontu
Gabriela
G
Wicha
Max S
MS
D001943:Breast Neoplasms / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology*; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
D051880:Receptors, Notch; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins