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HOUSTON -- (February 29, 2008) -- High levels of the enzyme atypical
protein kinase C (aPKC) increases the activity of the cancer-associated
protein steroid receptor coactivator-3 (SRC-3) in cancer cells that
depend on estrogen to promote their growth, said researchers at Baylor
College of Medicine in Houston in a report that appears in the current
issue of the journal Molecular Cell.
"This finding has implications for better understanding diseases
such as breast cancer," said Dr. Bert O'Malley, chair of molecular and
cellular biology at BCM and senior author of the report that
investigated the relationship between SRC-3 and the enzyme.
Results link aPKC with cancer
Atypical protein kinase C is frequently found at high levels in
tumors as is SRC-3. In this study by BCM researchers, experiments
demonstrated that the enzyme activates and stabilizes (through adding a
phosphate molecule) the coactivator SRC-3 in a way that makes it
dependent on the presence of a cellular receptor for the hormone
estrogen.
"These results link the aPKC with cancer initiation and growth that
is dependent on estrogen," said O'Malley, also associate director of
basic science research in the Dan L. Duncan Cancer Center at BCM.
Kinases
This activity takes place in an acidic area of the SRC-3 molecule
and prevents the coactivator from being degraded, said O'Malley. This
is important because SRC-3 is known to induce cancer and to promote its
growth. Other studies had already demonstrated that other kinds of
kinases could degrade SRC-3.
"Kinases that stabilize SR-3 in cancer cells have not previously been reported," said O'Malley.
"We propose that when aPKC is overexpressed in cancer cells, the
consequence is increased SRC-3 function and powerful enhancement of
estrogen-receptor target gene transcription and promotion of
estrogen-dependent cell growth in cancer cells such as breast," he said.
Others who took part in the study include Ping Yi, Qin Feng, Larbi
Amazit David M. Lonard, Sophia Y. Tsai and Ming-Jer Tsai, all of BCM.
Funding for this work came from the National Institutes of Health,
the National Institute of Child Health and Human Development and the
U.S. Department of Defense Breast Cancer Research Program.
The article is available at http://www.molecule.org/
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