Cdk inhibitor p27Kip1 and hormone dependence in breast cancer.

Arteaga CL
Clin Cancer Res. 2004 10 (1 Pt 2): 368S-71S

PMID: 14734493 · DOI:10.1158/1078-0432.ccr-031204

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.

MeSH Terms (14)

Alleles Breast Neoplasms Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p27 Cytoplasm Cytosol Estrogens G1 Phase Humans Models, Genetic Prognosis Protein Processing, Post-Translational S Phase Tumor Suppressor Proteins

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