کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10956193 | 1098785 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Î4-tibolone
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Î4-tibolone Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Î4-tibolone](/preview/png/10956193.png)
چکیده انگلیسی
Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and 3β-OH-tibolone, and a delta-4 isomer (Î4-TIB) that has both androgenic and progestagenic properties. Here, we show that 5α-dihydrotestosterone (DHT) and Î4-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Î4-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Î4-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 382, Issue 2, 15 February 2014, Pages 899-908
Journal: Molecular and Cellular Endocrinology - Volume 382, Issue 2, 15 February 2014, Pages 899-908
نویسندگان
Tina Bianco-Miotto, Andrew P. Trotta, Eleanor F. Need, Alice M.C. Lee, Aleksandra M. Ochnik, Lauren Giorgio, Damien A. Leach, Erin E. Swinstead, Melissa A. O'Loughlin, Michelle R. Newman, Stephen N. Birrell, Lisa M. Butler, Jonathan M. Harris,