Question

5. Overexpression of SRC-3 compensates for its reduced affinity for the tamoxifen-bound estrogen receptor. Determine if the following alternative hypotheses are also consistent with the development of chemoresistance.

are the following consistent or inconsistent?

The estrogen receptor mutates to reduce affinity for tamoxifen but not estradiol.	?
SRC-3 mutates to gain affinity for the ER-tamoxifen complex	?
The estrogen response element mutates to reduce affinity for the estrogen receptor.	?
Estradiol levels increase.	?

Answer 1

SRC act as as activator of estrogen receptor ( ER) thus by binding to ER tamoxifen complex its antagonize the effects of tamoxifen and invovle in development of chemoresistance.

Estrogen bind to ER receptor and bind to response element in DNA , promote cell growth and division and involve in breadt cancer . Here src act as co activator of ER ( estrogen receptor). Tamoxifen bind to ER this bu interfere in binding to Response element in DNA prevent growth and divisions in cell . Based on this information we can solve the below problems.

1) The estrogen receptor mutates to reduce affinity for tamoxifen but not estradiol. - it receptor has reduced affinity for tamoxifen than it will lead to reduced binding or ER to tamoxifen and more ER will be free to bubd Response element and promote growth. It will lead to develop of chemoresistance.

Consistent with above hypothesis

2) S RC-3 mutates to gain affinity for the ER-tamoxifen complex

In this condition SRc complex will always bind to ER tamoxifen complex with high affinity and interfere in to tamoxifen function lead to chemoresistance

Consistent with above hypothesis

3) The estrogen response element mutates to reduce affinity for the estrogen receptor

If there is mutation in estrogen response element, than there will be reduced binding of estrogen ER complex to response element and reduced expression of gene .

It will lead to decreased chemoresistance.

It is inconsistent with the above hypothesis

4) estradiol level increased- increase chemoresistance

Consistent with above hypothesis