BackgroundEstrogen plays an important role in the development of estrogen-dependent breast carcinoma. Recently, several studies demonstrated a possible involvement of several micro RNAs (miRNAs) in the development of resistance to endocrine therapy in breast cancer patients, but the correlation between estrogen actions and miRNA expression in breast carcinoma still remains largely unknown. Therefore, in this study, we examined the in vitro effects of estrogen upon miRNA expression profiles in breast carcinoma.MethodsWe first screened the miRNA expression profiles induced by 17β-Estradiol (E2) using RT2 miRNA PCR Array in the ER-positive breast carcinoma cell line MCF-7. We identified miR-7 as the important miRNA associated with estrogen actions in these cells and further examined the changes of estrogen-dependent EGFR expression by miR-7 in ER-positive or -negative breast carcinoma cell lines including MCF-7. We also evaluated the correlation between miR-7 and EGFR expression in breast carcinoma cells derived from 21 patients using laser capture microdissection combined with quantitative reverse transcriptase-PCR.ResultsSeventeen miRNAs were significantly induced by E2 treatment in the MCF-7 cell line. Among 17 miRNAs induced by estradiol treatment, only miR-7 expression was significantly decreased by subsequent ICI treatment. The expression of miR-7 was up-regulated 2.94-fold by E2 treatment. miR-7 was reported to suppress epidermal growth factor receptor (EGFR) expression in several human malignancies. Transfection of miR-7 significantly suppressed EGFR mRNA levels in MCF-7 cells. Depletion of E2 from cell culture media also increased the expression level of EGFR mRNA in MCF-7 and T-47D cells but not in ER-negative, MDA-MB-231 and SK-BR-3 cells. We also evaluated the status of miR-7 in breast carcinoma tissues, but the correlation between the status of miR-7 and EGFR in carcinoma cells isolated by laser capture microscopy was not detected.ConclusionsThese results suggest that miR-7 may play a role in the development of resistance to endocrine therapy in breast cancer patients through regulating EGFR expression of carcinoma cells.
What ' s known on the subject? and What does the study add? Localization of PDE9 in human LUT has not been reported in the literature, although PDE5 was reported to be abundantly present only in smooth muscle cells using immunohistochemistry. This is the fi rst reported study which demonstrated the expression of PDE9 in the urothelium and neuron cells in the intramural ganglia of human LUT. Patterns of PDE9 localization were clearly different from those of PDE5, which suggest that functions of PDE9 were therefore considered to be different from those of PDE5 in human LUT.
OBJECTIVES• To examine the roles of the one of the cyclic guanosine monophosphate (cGMP)-specifi c phosphodiesterases (PDEs), PDE9, in human lower urinary tract (LUT), we performed immunohistochemistry (IHC) using autopsy specimens.• To demonstrate the potential functional differences between PDE5 and PDE9 in human LUT, the localization of PDE5 and PDE9 was also compared using lasercapture microdissection (LCM)/reverse transcriptase-polymerase chain reaction (RT-PCR) method.
MATERIALS AND METHODS• We immunolocalized PDE9 in human bladder (60 cases) and prostate (40) specimens using IHC.• We performed LCM/RT-PCR evaluation in six human bladders to determine the differential expression patterns of PDE5 and PDE9.
RESULTS• PDE9 immunoreactivity was detected in the bladder urothelium of all the cases and in 85% of the prostatic urethral urothelium.• PDE9 immunoreactivity was detected in the perikaryon of the intramural ganglia.• LCM/RT-PCR evaluation showed that PDE5 mRNA was exclusively detected in smooth muscle cells but PDE9 mRNA was mainly detected in the urothelium of the human bladder.
CONCLUSION• PDE9 is widely distributed in the urothelial epithelium of the human LUT and its potential roles may be different from those of PDE5.
These results all indicated that when analyzing miRNAs in surgical pathology specimens of breast cancer as a biomarker, they should be examined as a cluster through miRNA profiling, rather than relying on the analysis of a single miRNA.
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