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Role Of Estrogen In Breast-Cancer

by Medindia Content Team on  September 9, 2005 at 2:57 PM Cancer News   - G J E 4
Role Of Estrogen In Breast-Cancer
Scientists have been wondering how estrogen -dependent breast-cancer cells grow and spread rapidly. Recent research on the above area has revealed that the depletion of estrogen is associated with loss of regulatory protein.
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The scientists report that human breast-cancer cells exposed to estrogen in their laboratory showed a dramatic reduction in numbers of a crucial nuclear receptor corepressor, a protein known as N-CoR . They also found that the anti-estrogen drug tamoxifen, often used in breast-cancer treatments, encouraged N-CoR recovery, a beneficial activity.

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Because estrogen has the ability to reduce the levels of N-CoR, it can promote the associated proliferation and progression of breast cancer, as the balance of co-activators and co-repressors involved in normal gene transcription is altered.

The findings may have sweeping implications. For one, the mechanisms at play could explain at least some of the mixed results seen in women using estrogen and progesterone in hormone therapy.

While numbers of N-CoR proteins fell to 20 percent of normal, the level of N-CoR's messenger RNA went untouched. The reduction of N-CoR followed an up regulation of the ubiquitin ligase Siah2, an enzyme that targets certain proteins for degradation.

This "secondary effect" may have broad implications for other important cellular activities. Reductions in N-CoR over time also could promote cancer development in other sites, such as the uterus, and could adversely affect the desired activities of vitamin D, retinoid and thyroid receptors.

The study sheds light on the impact of estrogen on certain cells, as well as how tamoxifen works as an anti-estrogen to facilitate recovery of N-CoR. Understanding more of the mechanisms involved could lead to the development of other related agents that might reduce some of the unwanted side effects of tamoxifen, such as stimulation of the uterus.
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