UTSW study reveals how estrogen drives breast cancer cell growth

By Jan Jarvis

Photo of Dr. Kraus
Dr. W. Lee Kraus

A new study led by a UT Southwestern Medical Center researcher provides a clearer picture of how estrogen drives cell growth in breast cancer.

The study published April 25 in Molecular Cell details how estrogen activates genes in breast cancer cells and the rate at which it does so, said Dr. W. Lee Kraus, Director of the Cecil H. and Ida Green Center for Reproductive Biology Sciences at UT Southwestern and corresponding author of the study.

“We are able to understand in a very fundamental, detailed, and quantitative way how estrogen is acting at the molecular level,” said Dr. Kraus, also Professor of Obstetrics and Gynecology, and Pharmacology. “This gives us a way to understand estrogen’s role in breast cancers and how the whole process goes wrong during the course of the disease.”

It long has been known that estrogen plays an important role in breast cancer cells, driving the uncontrolled growth of the cells by activating key growth-regulating genes. About two-thirds of breast cancers contain estrogen receptors, the proteins that allow the cell to respond to the hormone as a mitogenic, or growth-promoting, signal.

In cells, an enzyme called RNA polymerase “reads” the DNA in the genome and transcribes it into messenger RNA molecules, which serve as instructions for making proteins. The rate at which genes are transcribed by RNA polymerase determines the levels of mRNAs, ultimately controlling the levels of proteins and, hence, the biology of the cells.

Using state-of-the-art molecular, genomic, and computational techniques, Dr. Kraus and his team of collaborators, including lead author Dr. Charles Danko from Cornell University, were able to determine the rate of gene transcription for hundreds of genes activated by estrogen. They found that estrogen activates genes using a different set of molecular mechanisms than other cellular signaling pathways. Dr. Danko also is a postdoctoral researcher in Dr. Kraus’ lab.

“These studies are allowing us to distinguish the different ways signals turn genes on in different cell types, which really determines physiological outcomes in those cells,” Dr. Kraus said. “This allows us to understand how estrogen and other parallel signaling pathways control the biology of breast cancer.”

This knowledge could help researchers develop drugs that block the process and lead to new therapeutic interventions for breast cancer. The research also could provide a model for better understanding the biology of other types of cancer.

Also working on the study for UT Southwestern was Xin Luo, a graduate student in Dr. Kraus’ lab.

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Dr. Kraus holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences.

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