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Cell Cycle. 2014;13(8):1256-64. doi: 10.4161/cc.28156. Epub 2014 Feb 17.

CAPER, a novel regulator of human breast cancer progression.

Author information

1
Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA; Department of Pharmaceutical Sciences; Philadelphia College of Pharmacy; University of the Sciences in Philadelphia; Philadelphia, PA, USA.
2
Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
3
Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA; Breakthrough Breast Cancer Research Unit; Institute of Cancer Sciences; University of Manchester; Manchester, UK.
4
Breakthrough Breast Cancer Research Unit; Institute of Cancer Sciences; University of Manchester; Manchester, UK.
5
Department of Cancer Biology; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.

Abstract

CAPER 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 CAPER in human breast cancer specimens. We demonstrated that CAPER was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPER 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 CAPER in human breast cancer initiation and progression remained unknown. Here, we used a lentiviral-mediated gene silencing approach to reduce the expression of CAPER in the ER-positive human breast cancer cell line MCF-7. The proliferation and tumorigenicity of MCF-7 cells stably expressing control or human CAPER shRNAs was then determined via both in vitro and in vivo experiments. Knockdown of CAPER expression significantly reduced the proliferation of MCF-7 cells in vitro. Importantly, nude mice injected with MCF-7 cells harboring CAPER 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 CAPER shRNAs displayed reduced expression of the cell cycle regulators PCNA, MCM7, and cyclin D1, and the protein synthesis marker 4EBP1. In conclusion, knockdown of CAPER expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPER abrogated the activity of proliferative and protein synthesis pathways.

KEYWORDS:

CAPER; breast cancer; estrogen receptor; proliferation; tumor growth

PMID:
24621503
PMCID:
PMC4049962
DOI:
10.4161/cc.28156
[Indexed for MEDLINE]
Free PMC Article

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