Question

In: Biology

Estrogen-dependent breast cancer therapies (such as raloxifene) are focused on preventing activation of the estrogen response...

Estrogen-dependent breast cancer therapies (such as raloxifene) are focused on preventing activation of the estrogen response element (ERE). (1) Explain how estradiol (E2) activates the ERE and why this promotes tumor growth. (2) Identify three different targets (proteins) where drugs could bind to prevent estrogen-dependent cell growth, and explain how the protein-drug interaction blocks ERE activation in each case.

Solutions

Expert Solution

Ans 1) Estradiol(E2) activates the ERE or the Estrogen response element(ERE). The ER or the estrogen receptor is a ligand activated enhancer protein which has the ability to bind to specific DNA sequences called EREs that has high affinity and is able to take part in the whole of the gene expression. There are two ways the binding takes place. The first is either by direct binding where the E2 liganded ER binds to the specific sequence called as ERE which leads to the transcription. The second is the ER is able to interact with another DNA bound transcription factor which helps in stabilizing DNA binding of that particular transcription factor or it also leads to recruiting of the co-activators to complex. The binding of the ERE to the estradiol receptor lead to the formation of the breast tumor majorly that leads to uncontrolled proliferation of the cells. The estrogen promotes the formation of tumor due to the its binding to the ERE.

Ans 2) there are three target proteins at which the drugs can bind to prevent the estrogen dependent cell growth.

a)Human epidermal growth factor receptor 2 protein – It is also known as HER-2 which is expressed largely on the surface of cancer cells. Binding of the drug to this protein can stop the cell growth.

b) BRAF – It is a signaling proteins which leads to the progression of cancer. A drug binding to this target is also effective.

c) BCR-ABL fusion protein – This also drives to the formation of cancer and it helps in targeted cancer therapies.


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