breast cancer research • mcb as pre-med - The School of Molecular ...

daVId shaPIro
While it was known before that breast cancer cells have some way of dodging the immune system, it was Professor of Biochemistry in
MCB and Professor of Basic Medical Sciences at the College of Medicine David Shapiro who showed that estrogen contributes to that
process.
In cells containing the ER, the complex of estrogen and ER protein binds to specific DNA sequences to stimulate the production of
proteins involved in most breast cancers’ growth and evasion of the immune system.
“Since there already are good pharmaceuticals, such as tamoxifen, that work by competing with estrogens for binding to the receptor,
we wanted to target other binding sites on the ER,” Shapiro says. Using high-throughput screening techniques, Shapiro’s laboratory
was able to identify a compound that slowed the production of proteins that promote the growth of ER-positive breast cancer cells.
This compound works by triggering breast cancer cells to destroy ER protein, blocking the action of estrogen, and preventing the
growth of cancer cells. This process stops the growth of breast cancer cells that contain ER — even those that are resistant to tamoxifen
— and has little effect on other cell types.
In an important cell culture test of the new compound in a system in which breast cancer cells form colonies that resemble minitumors,
the compound completely blocked colony formation. The next steps are testing the compound in an animal model, and
identifying how it triggers the cells to destroy ER protein.
Drug development, a new direction for Shapiro’s lab, capitalizes on the recent establishment of a screening center by Shapiro and
several faculty members. With its robotic instruments and library of 170,000 compounds, the screening facility plays a key role in the
lab’s ability to rapidly test and identify new compounds with promising anti-cancer activity.
Shapiro notes that MCB has a national and international reputation for its community of experts looking at breast cancer from a variety
of directions. “We have lots of first-hand technical knowledge that we share, which makes doing experiments a lot easier,” he says.
8 . mcb
“Undergraduate pre-med students Kenneth Berg and Amanda
Etheridge are working to identify the chemical structures that make
a compound a specific inhibitor of estrogen receptor in breast cancer
cells.”—David Shapiro on two of the students who work in his lab