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Lmw-E Mediates Mammary Tumorigenesis By Deregulating Acinar Morphogenesis & Generating Cancer Stem Cells, Mylinh T. Duong
Lmw-E Mediates Mammary Tumorigenesis By Deregulating Acinar Morphogenesis & Generating Cancer Stem Cells, Mylinh T. Duong
Dissertations & Theses (Open Access)
Cyclin E is the regulatory subunit of the cyclin E/CDK2 complex that
mediates the G1-S phase transition. N-terminal cleavage of cyclin E by elastase in
breast cancer generates two low molecular weight (LMW) isoforms that exhibit both
enhanced kinase activity and resistance to p21 and p27 inhibition compared to fulllength cyclin E. Clinically, approximately 27% of breast cancer patients overexpress
LMW-E and associate with poor survival. Therefore, we hypothesize that LMW-E
disrupts normal mammary acinar morphogenesis and serves as the initial route into
breast tumor development. We first demonstrate that LMW-E overexpression in
non-tumorigenic hMECs is sufficient to induce tumor …