Mercier, I, Gonzales, DM, Quann, K, Pestell, TG, Molchansky, A, Sotgia, Federica, Hulit, J, Gandara, R, Wang, C, Pestell, RG, Lisanti, MP and Jasmin, J 2014, 'CAPER, a novel regulator of human breast cancer progression' , Cell Cycle, 13 (8) , pp. 1256-1264.
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CAPE R is an estrogen receptor (ER) co-activator that was recently shown to be involved in human breast cancer pathogenesis. Indeed, we reported increased expression of CAPE R in human breast cancer specimens. We demonstrated that CAPE R was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPE R was expressed at higher levels in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specimens, where it assumed a predominantly nuclear distribution. However, the functional role of CAPE R in human breast cancer initiation and progression remained unknown. Here, we used a lentiviral-mediated gene silencing approach to reduce the expression of CAPE R in the ER-positive human breast cancer cell line MCF-7. The proliferation and tumorigenicity of MCF-7 cells stably expressing control or human CAPE R shRNAs was then determined via both in vitro and in vivo experiments. Knockdown of CAPE R expression significantly reduced the proliferation of MCF-7 cells in vitro. Importantly, nude mice injected with MCF-7 cells harboring CAPE R shRNAs developed smaller tumors than mice injected with MCF-7 cells harboring control shRNAs. Mechanistically, tumors derived from mice injected with MCF-7 cells harboring CAPE R shRNAs displayed reduced expression of the cell cycle regulators PCNA, MCM7, and cyclin D1, and the protein synthesis marker 4EBP1. In conclusion, knockdown of CAPE R expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPE R abrogated the activity of proliferative and protein synthesis pathways.
|Schools:||Schools > School of Environment and Life Sciences > Biomedical Research Centre|
|Journal or Publication Title:||Cell Cycle|
|Publisher:||Taylor and Francis|
|Funders:||Funder not known|
|Depositing User:||Federica Sotgia|
|Date Deposited:||05 Jul 2016 09:58|
|Last Modified:||05 Jul 2016 09:58|
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