Helix-loop-helix proteins in mammary gland development and breast cancer.
The basic helix-loop-helix (bHLH) family of transcription factors functions in the coordinated regulation of gene expression, cell lineage commitment, and cell differentiation in most mammalian tissues. Helix-loop-helix Id (Inhibitor of DNA binding) proteins are distinct from bHLH transcription factors in that they lack the basic domain necessary for DNA binding. Id proteins thus function as dominant negative regulators of bHLH transcription factors. The inhibition of bHLH factor activity by forced constitutive expression of Id proteins is closely associated with the inhibition of differentiation in a number of different cell types, including mammary epithelial cells. Moreover, recent literature suggests important roles of HLH proteins in many normal and transformed tissues, including mammary gland. Therefore, future directions for prognosis or therapeutic treatments of breast cancer may be able to exploit bHLH and Id genes as useful molecular targets. The purpose of this review is to summarize the evidence implicating HLH proteins in the regulation of normal and transformed mammary epithelial cell phenotypes.
Desprez
Pierre-Yves
PY
California Pacific Medical Center, Cancer Research Institute, San Francisco, California 94115, USA. pdesprez@cooper.cpmc.org
Sumida
Tomoki
T
Coppé
Jean-Philippe
JP
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D008321:Mammary Glands, Animal / Q000196:embryology*; D042361:Mammary Glands, Human / Q000196:embryology*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008954:Models, Biological; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011487:Protein Conformation; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497450:ID2 protein, human; C490128:ID4 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D012097:Repressor Proteins; D014157:Transcription Factors