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FXR could slow growth of Tamoxifen-resistant cancer cells. - By: Rick Dahne

A new FXR (farnesoid X receptor) antibody study has revealed that activation of the FXR protein could slow the growth of breast cancer cells resistant to Tamoxifen. The FXR products as seen on our antibody database have previously been used to show that FXR reduces proliferation of breast cancer cells. However, it was not known if it would have the same effect on Tamoxifen-resistant tissue.

FXR is a nuclear receptor that is mainly found in hepatic tissue. Following a recent revelation that it is also found in breast cancer cells, it has become a focus of research in this area.

One of the steroid receptor superfamily, FXR (also called NR1H4, or nuclear receptor subfamily 1/group H-4) binds to a class of lipids called farnesoids, at DNA sequences known as hormone response elements (HREs). Activation by bile acid ligands is followed by translocation to the nucleus, where a heterodimer is formed with RXR, a promiscuous mediator which dimerises with a number of proteins.

Antibody studies have shown the primary function of FXR is to suppress CYP7A1 (cholesterol 7 alpha-hydroxylase) via a negative feedback pathway, thus regulating bile salt levels. Its expression in breast cancer cells, and its effect on controlling their growth, led to a study to see its effect on cells resistant to the cancer drug Tamoxifen.

Two cell-lines were used: MCF-7TR, which is tamoxifen-resistant, and MCF-7, which is sensitive. The findings indicated that FXR slowed cell proliferation, irrespective of whether the cells were tamoxifen-resistant or not. In fact, the effect was enhanced in the resistant cells.

The study suggests that FXR works by inhibiting expression of the growth factor signalling mediator HER2, which is over-expressed in breast cancer cells, disrupting growth regulation and leading to enhanced malignancy. Tamoxifen-resistant cells appear to have a greater dependency on HER2, explaining why FXR had a greater effect on these cells.

We at Novus Biologicals have a broad antibody database covering breast cancer research, to which we are adding all the time.

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