IGF-1 Regulates Cyr61 Induced Breast Cancer Cell Proliferation and Invasion.
In: PLoS ONE, Jg. 9 (2014-07-01), Heft 7, S. 1-11
Online
academicJournal
Zugriff:
Background: Studies from our laboratory and others have shown that cysteine-rich 61 (Cyr61) may be involved in tumor proliferation and invasion. In earlier studies, we demonstrated increased insulin-like growth factor-I (IGF-1) is associated with breast tumor formation and poor clinical outcomes. In our current study we have investigated IGF-1 regulation of Cyr61 and whether targeting IGF-1 could inhibit Cyr61 induced tumor growth and proliferation. Methods: Several ATCC derived normal and breast cancer cell lines were used in this study: MDA-MB231, BT474, MCF-7, and SKBR3. We also tested cells stably transfected in our laboratory with active Akt1 (pAkt; SKBR3/AA and MCF-7/AA) and dominant negative Akt1 (SKBR3/DN and MCF-7/DN). In addition, we used MCF-7 cells transfected with full length Cyr61 (CYA). Monolayer cultures treated with IGF-1 were analyzed for Cyr61 expression by RT-PCR and immunohistochemical staining. Migration assays and MTT based proliferation assays were used to determine invasive characteristics in response to IGF-1/Cyr61 activation. Results: Cells with activated Akt have increased levels of Cyr61. Conversely, cells with inactive Akt have decreased levels of Cyr61. IGF-1 treatment increased Cyr61 expression significantly and cells with high level of Cyr61 demonstrate increased invasiveness and proliferation. Cyr61 overexpression and activation led to decrease in E-cadherin and decrease in FOXO1. Inhibition of the PI3K and MAPK pathways resulted in significant decrease in invasiveness and proliferation, most notably in the PI3K pathway inhibited cells. Conclusion: The findings of this study show that IGF-1 upregulates Cyr61 primarily through activation of the Akt-PI3K pathway. IGF-1 induced MAPK plays a partial role. Increase in Cyr61 leads to increase in breast cancer cell growth and invasion. Hence, targeting Cyr61 and associated pathways may offer an opportunity to inhibit IGF-1 mediated Cyr61 induced breast cancer growth and invasion. [ABSTRACT FROM AUTHOR]
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IGF-1 Regulates Cyr61 Induced Breast Cancer Cell Proliferation and Invasion.
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Autor/in / Beteiligte Person: | Sarkissyan, Suren ; Sarkissyan, Marianna ; Wu, Yanyuan ; Cardenas, Jessica ; Koeffler, H. Phillip ; Vadgama, Jaydutt V. |
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Zeitschrift: | PLoS ONE, Jg. 9 (2014-07-01), Heft 7, S. 1-11 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0103534 |
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