title: CAPER, a novel regulator of human breast cancer progression.
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.
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mercier
authors.affiliation: Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Gonzales
authors.affiliation: Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Quann
authors.affiliation: Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Pestell
authors.affiliation: Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Molchansky
authors.affiliation: 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.
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.affiliation: Breakthrough Breast Cancer Research Unit; Institute of Cancer Sciences; University of Manchester; Manchester, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hulit
authors.affiliation: Breakthrough Breast Cancer Research Unit; Institute of Cancer Sciences; University of Manchester; Manchester, UK.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gandara
authors.affiliation: Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cancer Biology; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.affiliation: 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.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jasmin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014176:Protein Biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C084105:HCC1 autoantigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
keywords: CAPER; breast cancer; estrogen receptor; proliferation; tumor growth