Cyclin E both regulates and is regulated by calpain 2, a protease associated with metastatic breast cancer phenotype

Stephen J. Libertini, Brian S. Robinson, Navdeep K. Dhillon, Danielle Glick, Michael George, Satya Dandekar, Jeffrey Gregg, Earl Sawai, Maria Mudryj

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Overexpression of cyclin E in breast tumors is associated with a poor response to tamoxifen therapy, greater genomic instability, more aggressive behavior, and a poor clinical prognosis. These tumors also express low molecular weight isoforms of cyclin E that are associated with higher kinase activity and increased metastatic potential. In the current study, we show that cyclin E overexpression in MCF7 cells transactivates the expression of calpain 2, leading to proteolysis of cyclin E as well as several known calpain substrates including focal adhesion kinase (FAK), calpastatin, pp60src, and p53. In vivo inhibition of calpain activity in MCF7-cyclin E cells impedes cyclin E proteolysis, whereas in vivo induction of calpain activity promotes cyclin E proteolysis. An analysis of human breast tumors shows that high levels of cyclin E are coincident with the expression of the low molecular weight isoforms, high levels of calpain 2 protein, and proteolysis of FAK. Lastly, studies using a mouse model of metastasis reveal that highly metastatic tumors express proteolyzed cyclin E and FAK when compared to tumors with a low metastatic potential. Our results suggest that cyclin E-dependent deregulation of calpain may be pivotal in modifying multiple cellular processes that are instrumental in the etiology and progression of breast cancer.

Original languageEnglish (US)
Pages (from-to)10700-10708
Number of pages9
JournalCancer Research
Issue number23
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


Dive into the research topics of 'Cyclin E both regulates and is regulated by calpain 2, a protease associated with metastatic breast cancer phenotype'. Together they form a unique fingerprint.

Cite this