Publication date: Available online 20 June 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Xiao-Qiang Wang, Juliette A. Aka, Tang Li, Dan Xu, Charles J. Doillon, Sheng-Xiang Lin
17beta-hydroxysteroid dehydrogenase type 7 (17β-HSD7) promotes breast cancer cell growth via dual-catalytic activity by modulating estradiol and DHT. Here, we clarified the expression pattern of 17β-HSD7 in postmenopausal luminal A type breast cancer with The Cancer Genome Atlas (TCGA) cohort. The impact of 17β-HSD7 inhibition on the proteome of MCF-7 cells was investigated and on cell apoptosis was revealed. MCF-7 cells were treated with an efficient inhibitor of 17β-HSD7 or with vehicle, and a differential proteomics study was performed using two-dimensional (2D) gel electrophoresis followed by mass spectrometry and ingenuity pathway analysis (IPA). Cell apoptosis was analyzed by flow cytometry, followed by reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot to investigate the expression of apoptosis-related genes. Our data showed 17β-HSD7 is amplified in primary and progressive breast cancer, inhibition of 17β-HSD7 in MCF-7 cells modulated 104 proteins primarily involved in cell death/survival, cell growth and DNA processing. The expression of 78kDa glucose-regulated protein (GRP78) and anti-apoptosis factor Bcl-2 were significantly suppressed via 17β-HSD7 inhibition with INH7, consequently induced MCF-7 cell apoptosis. However, INH7 treatment of T47D, another widely used epithelial ER+ breast cancer cell line, led to an up-regulation of GRP78 expression, resulting in a limited increase in apoptosis. These results suggest cell-specific effects of INH7 in the breast cancer, which is interesting for further study. An combinatory effect on apoptosis by INH7 and Letrozole (aromatase inhibitor) was further demonstrated in MCF-7. Down-regulation of GRP78 via 17β-HSD7 inhibition enhances cell apoptosis in response to Letrozole. This study highlights GRP78 as a key regulator related to 17β-HSD7 inhibition and effect. Taken together, results from the present study suggest a hypothesis that inhibition of 17β-HSD7 would be a complementary strategy to Letrozole by suppression of GRP78 in ER+ breast cancer. However, from a research perspective, further studies have to be carried out with more breast cancer cell lines as well as in vivo model to assess the efficacy of inhibitor combination.
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Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Τετάρτη 21 Ιουνίου 2017
Inhibition of 17beta-hydroxysteroid dehydrogenase type 7 modulates breast cancer protein profile and enhances apoptosis by down-regulating GRP78
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- Corn silk maysin ameliorates obesity in vitro and ...
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- First case of anaphylaxis after botulinum toxin ty...
- A review of Acalypha indica L. (Euphorbiaceae) as ...
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- Antrodia cinnamomea sensitizes radio-/chemo-therap...
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- Clinical Features of Nivolumab-Induced Thyroiditis...
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- A Higher Ratio of Estradiol to Testosterone Is Ass...
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- Infestation of mites in external auditory canal
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- Is there an association between migraine and aller...
- June is National Dysphagia Awareness Month
- Results of endonasal dacryocystorhinostomy in pedi...
- Salivary epidermal growth factor concentrations in...
- Vocal fold hemorrhage into a physiologic sulcus
- A comparison of tonsillar surface swabbing, fine-n...
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- High Gpx1 expression predicts poor survival in lar...
- Infestation of mites in external auditory canal
- Positron-emission tomography enhancement after voc...
- Initial experience of a hereditary hemorrhagic tel...
- Is there an association between migraine and aller...
- June is National Dysphagia Awareness Month
- Endoscopic view of a dumbbell-shaped sphenoid fung...
- Results of endonasal dacryocystorhinostomy in pedi...
- Salivary epidermal growth factor concentrations in...
- Small airways disease and severe asthma
- Vocal fold hemorrhage into a physiologic sulcus
- WAO International Scientific Conference (WISC 2016...
- A comparison of tonsillar surface swabbing, fine-n...
- Training Surgical Residents With a Haptic Robotic ...
- PRELIM II(EDI BOARD)
- Accuracy of Fine Needle Cytology in Histological P...
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