Cdk inhibitor p27Kip1 and hormone dependence in breast cancer.
p27Kip1 is an important regulator of the G1 to S transition. While a potent inhibitor of cyclin-dependent-kinase (Cdk)2, p27 is also involved in assembly of cyclin D/Cdk4 complexes. Although rarely mutated, p27 is functionally downregulated in many human cancers by mechanisms involving enhanced degradation, cytoplasmic mislocalization, and/or sequestration by cyclin D/Cdk complexes in response to oncogenic signals. Therefore, low levels and/or cytoplasmic localized p27 have been associated with enhanced malignancy and poor patient prognosis in many neoplasias including breast cancer. Recent data discussed below suggest that a threshold of p27 is required for response to antiestrogens and, conversely, that low levels predict for antiestrogen resistance. These results imply that hormone receptor-positive tumors with low and/or cytosolic p27 respond poorly to antiestrogens and should be considered for alternative therapeutic strategies.
Arteaga
Carlos L
CL
Departments of Medicine and Cancer Biology and Breast Cancer Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. carlos.arteaga@vanderbilt.edu
D000483:Alleles; D001943:Breast Neoplasms / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000494:pharmacology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D008957:Models, Genetic; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D016196:S Phase; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D004967:Estrogens; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27