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How breast cancer cells evade therapeutic attacks
Date:3/31/2010

g the mechanisms involved in the indirect stimulation of ERα in cancer cells".

Researchers from his team have studied a molecule, cyclic AMP, which is able to convey various types of signals within the cell. Called a "second messenger", this molecule acts as an intermediary to transmit information between the exterior and the interior of the cell. Different growth factors, neurotransmitters or hormones, incapable of crossing the cell barrier, thus communicate their message by activating intracellular signalling pathways via cyclic AMP.

A novel mode of regulation

"During this project, we have studied how cyclic AMP could turn on ERα in breast cancer cells in the absence of estrogens", says lead author Sophie Carascossa. In this case, the second messenger triggers a specific biochemical signalling cascade in which a protein called CARM1 is involved. The protein then binds ERα and this in turn activates the receptor. "The interaction with CARM1 occurs in a domain of the receptor near the one that normally binds estrogens. This mode of regulation was completely unknown until now", specifies the scientist. The study also reveals that the signalling pathway is stimulated in a constitutive way in malignant cells resistant to tamoxifen, thus evading control in these cells.

Although the molecular mechanisms implicated in the resistance process are probably numerous, the interaction between CARM1 and ERα could represent a promising therapeutic target in the long run.


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Contact: Laura Pizurki
Lara.Pizurki@unige.ch
Cold Spring Harbor Laboratory
Source:Eurekalert

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