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; Jasmin, J

Abstract

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.

Citation

Mercier, I., Gonzales, D., Quann, K., Pestell, T., Molchansky, A., Sotgia, F., …Jasmin, J. (2014). CAPER, a novel regulator of human breast cancer progression. Cell Cycle, 13(8), 1256-1264. https://doi.org/10.4161/cc.28156

• Journal Article Type: Article
• Acceptance Date: Feb 9, 2014
• Online Publication Date: Feb 17, 2014
• Publication Date: Feb 17, 2014
• Deposit Date: Jul 5, 2016
• Journal: Cell Cycle
• Print ISSN: 1538-4101
• Electronic ISSN: 1551-4005
• Publisher: Taylor and Francis
• Volume: 13
• Issue: 8
• Pages: 1256-1264
• DOI: https://doi.org/10.4161/cc.28156
• Publisher URL: http://dx.doi.org/10.4161/cc.28156
• Additional Information: Funders : Funder not known