CAPER, a novel regulator of human breast cancer progression
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.
- Published Version
Restricted to Repository staff only
Download (3MB) | Request a copy
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|
Actions (login required)
|Edit record (repository staff only)|