HER-2/neu (erbB-2) and the cell cycle.
Signaling by the HER-2 proto-oncogene product results in the activation of several biochemical pathways, which in turn modulate the expression and function of cell cycle regulators. These alterations of cell cycle regulatory molecules may be critical for the conception and maintenance of the transformed phenotype conferred by HER-2 gene amplification and overexpression. On the other hand, blockade of HER-2 function with a therapeutic intent will require the reversal of these effects on cell cycle regulatory molecules in order for these interventions to be effective. Data is presented to suggest that the G1 cyclin D1 and the cyclin-dependent kinase inhibitor p27KIP1 may be involved in subversion of the G1/S traverse by signaling pathways activated by HER-2 function.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
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D
Busse
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Doughty
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CL
Arteaga
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D018734:Genes, erbB-2; D006801:Humans; D008869:Microtubule-Associated Proteins; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; C000715470:MAS1 protein, human; D008869:Microtubule-Associated Proteins; D000090063:Proto-Oncogene Mas; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27