Scientists Identify Inflammatory Circuit Which Triggers Breast Cancer

by Savitha C Muppala on  February 27, 2012 at 11:07 PM Cancer News   - G J E 4
Scientists have been able to identify the Inflammatory circuit which triggers breast cancer.
 Scientists Identify Inflammatory Circuit Which Triggers Breast Cancer
Scientists Identify Inflammatory Circuit Which Triggers Breast Cancer

Now, scientists from the Florida campus of The Scripps Research Institute have shed new light on exactly how the activation of a pair of inflammatory signaling pathways leads to the transformation of normal breast cells to cancer cells.

The scientists' discovery points to the activation of a self-sustaining signalling circuit that inhibits a specific RNA, a well-known tumour suppressor that helps limit the spread of cancer (metastasis).

Therapies that disable this circuit and halt this miRNA repression could have the potential to treat cancer.

In the new study, scientists identified the specific pathways that transform breast epithelial cells into active cancer cells.

The researchers, led by Jun-Li Luo, an assistant professor at Scripps Florida, found that immune/inflammatory cells ignite the transient activation of MEK/ERK and IKK/NF-kB pathways; the MEK/ERK pathway then directs a consistent activation of a signalling circuit in transformed cells.

This consistent signalling circuit maintains the malignant state of the tumour cells.

Luo compared this process to starting a car-a car battery starts the engine much like the transient signal activation turns on the consistent signal circuit.

Once the engine is started, it no longer needs the battery.

The scientists go on to show that the initial activation of these pathways also activates IL6, a cytokine involved in a number of inflammatory and autoimmune diseases, including cancer.

IL6 acts as a tumour initiator, sparking the self-sustaining circuit in normal breast cells necessary for the initiation and maintenance of their transformed malignant state.

In establishing that self-sustaining signal circuit, IL6 represses the action of microRNA-200c, which is responsible for holding down inflammation and cell transformation.

Since enhanced microRNA-200c expression impairs the growth of existing cancer cells and increases their sensitivity to anti-tumor drugs, compounds that disable microRNA-200c repression have the potential to act as a broad-spectrum therapeutic.

Interestingly, the new findings dovetail with the "multiple-hits theory" of tumour formation, which posits that once normal cells in the human body accumulate enough pre-cancerous mutations, they are at high-risk for transformation into tumour cells.

While the newly described initial pathway activation is momentary and not enough to cause any lasting changes in cell behaviour, it may be just enough to tip the cell's transformation to cancer, especially if it comes on top of an accumulation of other cellular changes.

The study has been published online by the journal Molecular Cell.

Source: ANI

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