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| Status |
Public on Jun 19, 2014 |
| Title |
DHT-AR, E2-AR and R5020-AR target gene profiles in LNCaP |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)α, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERα, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells.
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| Overall design |
Total RNAs from the LNCaP cells transfected with control siRNA (siCT) or siRNA for AR (siAR) transfected LNCaP cells before 24 hr followed by exposed to 10-7M of DHT, E2 or R5020 exposure for another 24 h, respectively, were used.
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| Contributor(s) |
Susa T, Okazaki T |
| Citation(s) |
25536295 |
| Submission date |
Jun 18, 2014 |
| Last update date |
Aug 21, 2019 |
| Contact name |
Takao Susa |
| E-mail(s) |
tsusa@med.teikyo-u.ac.jp
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| Organization name |
Teikyo University School of Medicine
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| Department |
Department of Biochemistry
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| Street address |
2-11-1, Kaga
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| City |
Itabashi-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
173-8605 |
| Country |
Japan |
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| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA253024 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE58615_RAW.tar |
98.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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