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A new protein is discovered to play a key role in cancer progression

NEW YORK, September 9, 2004 - Many cancers, including colon, prostate, and leukemia, continue to grow unchecked because they do not respond to a signal to die and stop proliferating from Transforming Growth Factor-beta (TGF-b). The cause of this signaling disruption of the normal cell cycle has not been fully understood. For the first time, scientists at Memorial Sloan-Kettering Cancer Center have discovered the biologic function of the cytoplasmic form of the Promyelocytic Leukemia protein (PML), and identified it as an essential factor in maintaining TGF-b signaling. Their findings, published in the September 9 issue of the journal Nature, explain the link between these two proteins in the development of cancer and suggest that restoring their activity may provide a possible cancer treatment.

"Through our discovery of the biologic function of PML and its essential role in maintaining TGF-b signaling, we can better understand the progression of many human cancers," said Pier Paolo Pandolfi, M.D., Ph.D., Head of the Molecular and Developmental Biology Laboratory at Memorial Sloan-Kettering and the study's senior author. "Restoring PML function may correct this signaling defect therefore providing a novel therapeutic target for cancer drugs."

TGF-b is a protein that can suppress tumor development by signaling a cell to stop growing. The unresponsiveness to TGF-b signaling has been associated with a variety of human cancers. In addition to this loss of TGF-b, loss of PML is associated with tumor progression in many human cancers, including prostate, breast, colon, and lung, as shown by Dr. Pandolfi and colleagues in a recently published study in the Journal of the National Cancer Institute. In a later work published in Nature Cell Biology, they also demonstrated an unexpected role for PML in affecting the nucleolar network for tumor suppression and in regulating the function of a gene crucial to the suppression of the genesis of cancer.


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Contact: Joanne Nicholas
mediastaff@mskcc.org
212-639-3573
Memorial Sloan-Kettering Cancer Center
8-Sep-2004


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