Abstract
Too Much Cleavage of Cyclin E Promotes Breast Tumorigenesis
Highlights
Five isoforms of cyclin E, ranging in size from 33 to 44 kDa, have been identified in tumors over-expressing cyclin E
In comparison to fulllength cyclin E (50 kDa), low molecular weight forms of cyclin E (LMW-E) forms are uniquely expressed in tumor cells, exhibit enhanced cyclin-dependent kinase 2 (CDK2)-associated kinase activity, have increased affinity for CDK2 [7,8,9], and exhibit decreased inhibition by CDK2 inhibitors, p21 and p27 (Figure 1) [10,11]
Both high LMW-E levels and up-regulation of the b-RAF-ERK1/2-mTOR signaling pathway are associated with poor survival, suggesting functional correlation of these events in aggressive tumors
Summary
Five isoforms of cyclin E, ranging in size from 33 to 44 kDa, have been identified in tumors over-expressing cyclin E. In comparison to fulllength cyclin E (50 kDa), LMW-E forms are uniquely expressed in tumor cells, exhibit enhanced CDK2-associated kinase activity, have increased affinity for CDK2 [7,8,9], and exhibit decreased inhibition by CDK2 inhibitors, p21 and p27 (Figure 1) [10,11]. Ectopic expression of LMW-E in immortalized hMECs promotes tumorigenesis in xenografts and transgenic mice to a much greater extent than full-length cyclin E.
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