Discovery sheds light on how cells progress to more aggressive forms.(Brief Article)

2002 SEP 26 - (NewsRx.com & NewsRx.net) -- Despite recent advances in breast cancer treatment that have led to long-term survival for millions of women, most tumors eventually stop responding to standard therapies.

The result is a poor prognosis for the patient and frustration for doctors who must turn to investigational therapies in hope of slowing the progression of the disease.

But now researchers at The University of Texas M.D. Anderson Cancer Center have begun to understand how breast cancer cells suddenly stop responding to treatment and become more aggressive. The finding, which appears in the journal Nature, points to a potential target that in principle, may reverse the process and restore hormone responsiveness to breast cancer cells.

A research team led by Dr. Rakesh Kumar, professor of cellular and molecular oncology, reports discovering a new form of a protein that is associated with aggressive forms of cancer, including breast cancer. The new protein, termed MTA1s (metastatic tumor antigen 1, short version), appears to intercept the key protein receptor that is responsible for communicating with the female hormone estrogen inside cells.

An estimated 192,200 women will be diagnosed with invasive breast cancer and 40,200 women will die this year, according to the American Cancer Society. About 60% of breast cancers are classified as estrogen receptor-positive by conventional evaluation methods, meaning that they respond to signals from the female hormone estrogen through its receptor. These patients typically respond well to hormonal treatment with tamoxifen and other antiestrogenic compounds, which block estrogen signals that tell the cancer cells to multiply.

But after a period of time, some breast cancer cells suddenly become hormone-independent, growing and multiplying more rapidly, even in the presence of antiestrogen treatment. Physicians typically determine hormone responsiveness by looking for the estrogen receptor molecule in the cell's nucleus. When estrogen receptors can no longer be found in the nucleus, the cancer cell is termed "hormone independent" and other types of therapy must be tried.

"The underlying molecular mechanisms for aggressive tumor behavior and estrogen receptor-negative tumors are poorly understood, and this is an area of intense research," Kumar said. "This research is an important step toward understanding how breast cancers become hormone-independent. With greater understanding, we can design new therapies to ...