Tumor Cells Replace The Need For Growth Factors By Using Other Stimulators

One feature of tumor cells that makes them cancerous is their ability to grow in the absence of the signals that normal cells require to grow. For example, breast cancer is often associated with the ability of the tumor cells to grow in the absence of a growth factor known as EGF. In many cases, the tumor cells become independent of EGF through genetic mutations that result in the receptor for EGF or its downstream signaling proteins becoming constantly activated. However, a study using a human breast cancer cell line, which appears online on January 11 in advance of publication in the February print issue of the Journal of Clinical Investigation, shows that increased amounts of another molecule that can activate the EGF receptor (TGF-alpha) can also cause the tumor cells to become independent of EGF.

Mina Bissell and Paraic Kenny from the University of California, Berkeley, showed that a human breast cancer cell line expressed high levels of TGF-alpha, which can bind and activate the EGF receptor. Expression of high levels of TGF-alpha required a protein known as TACE, which cleaves a precursor form of TGF-alpha to generate the active form of the protein, and inhibition of TACE impaired the tumorigenic potential of the breast cancer cell line. Importantly, high levels of expression of TGF-alpha and TACE were found to correlate with and be predictive of a poor outcome in patients with breast cancer. This study therefore identifies a new pathway by which tumor cells can become independent of EGF, and the authors suggest that targeting this pathway might provide a new approach to treating breast cancer and other cancers in which the tumor cells grow independently of EGF, such as colon cancer.

TITLE: Targeting TACE-dependent EGFR ligand shedding in breast cancer

AUTHOR CONTACT:

Mina J. Bissell
University of California, Berkeley, California, USA.

Paraic A. Kenny
University of California, Berkeley, California, USA.

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JCI table of contents -- January 11, 2006

Contact: Karen Honey
Journal of Clinical Investigation