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Drugs targeting chromosomal instability may fight a particular breast cancer subtype
Date:2/6/2012

PHILADELPHIA -- Another layer in breast cancer genetics has been peeled back.

A team of researchers at Jefferson's Kimmel Cancer Center (KCC) led by Richard G. Pestell, M.D., PhD., FACP, Director of the KCC and Chair of the Department of Cancer Biology, have shown in a study published online Feb. 6 in the Journal of Clinical Investigation that the oncogene cyclin D1 may promote a genetic breakdown known as chromosomal instability (CIN). CIN is a known, yet poorly understood culprit in tumor progression.

The researchers used various in vitro and in vivo model systems to show that elevated levels of cyclin D1 promotes CIN and correlate with CIN in the luminal B breast cancer subtype. Cyclin D1 protein is elevated in breast, prostate, lung and gastrointestinal malignancies.

The findings suggest that shifting towards drugs targeting CIN may improve outcomes for patients diagnosed with luminal B subtype. Luminal B breast cancer has high proliferation rates and is considered a high grade malignancy.

Estrogen or progesterone receptor positive and HER2 positive cancers indicate luminal B, and about 10 percent of patients are diagnosed with it every year, though many do not respond well to treatment. The identification of CIN in luminal B provides a new therapeutic opportunity for these patients.

"Cyclin D1 has a well defined role in cell proliferation through promoting DNA replication," says Dr. Pestell. "My team was the first to discover that cyclin D1 also has alternate functions, which include regulating gene transcription at the level of DNA. We were interested in discovering the function of DNA associated cyclin D1."

To help answer this, the researchers, including lead author Mathew C. Casimiro, Ph.D., of the Department of Can
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Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert  

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