THE ROLE OF DMP1 IN HUMAN BREAST CANCER PROGNOSIS AND CYCLIN D1-INDUCED BREAST CANCER

Dmp1 is a transcriptional factor that directly binds and activates the Arf promoter. It is also a bona fide tumor suppressor that is activated by oncogenic Ras and HER2 signalings and in turn stimulates the Arf-p53 tumor suppression pathway. Dmp1 physically interacts with cyclin D1 that is frequently overexpressed in breast cancer. Cyclin D1 can either increase or decrease the transcriptional activity of Dmp1 depending the molecular contexts of the targeted genes. Although loss of Dmp1 significantly accelerated oncogenic neu induced mammary carcinogenesis in mice, the role of DMP1in human breast cancer needs to be indentified. In addition, the biological functions and significance of Dmp1-Cyclin D1 interaction in breast cancer remains to be explored. In Chapter II, we show that the LOH of the DMP1 locus was found in 42% of human breast carcinomas, and the LOH of INK4a/ARF and p53 were found in 20% and 34% of the cases, respectively. The LOH of DMP1 was mutually exclusive from that of INK4a/ARF and p53 and it was associated with the luminal A category and longer relapse-free survival. Conversely, both Hdm2 amplification and p53 LOH were associated with shorter survival, while the LOH of INK4a/ARF had no prognostic value in breast cancer.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2013

Author dc:creator

• Zhu, Sinan

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/39033

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/39033