title: ARC (apoptosis repressor with caspase recruitment domain) is a novel marker of human colon cancer.
abstract: The ability of cells to escape apoptosis is critical for carcinogenesis as well as resistance to radiation and chemotherapy. ARC (Apoptosis Repressor with CARD (caspase recruitment domain)) is an unusual inhibitor of apoptosis in that it antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. ARC is expressed predominantly in terminally differentiated cells such as cardiac and skeletal myocytes and neurons. Recently, however, the abundance of ARC was noted to be markedly increased in the epithelium of primary human breast cancers compared with benign breast tissue and to confer chemo- and radiation-resistance. Whether the induction of ARC is specific to breast cancer or a more general feature of neoplasia remains unknown. In this study, we assessed the abundance and subcellular localization of ARC in 21 human colon cancer cell lines and in 44 primary human colon adenocarcinomas and adjacent benign colonic tissue. ARC was present at high levels in most colon cancer cell lines and in almost all primary colon cancers compared with corresponding controls. Levels of ARC in the cytoplasm were increased in well, moderately, and poorly differentiated cancers compared with benign tissue, while levels of nuclear ARC were increased only in moderately differentiated tumors. Moreover, epithelial cancers of the ovary and cervix exhibited increased ARC abundance compared with controls. These results demonstrate that ARC is a novel marker of human colon cancer and suggest that it may be a general feature of epithelial cancers.
authors.affiliation: Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mercier
authors.forename: Magalis
authors.initials: M
authors.lastname: Vuolo
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Jasmin
authors.forename: Christina M
authors.initials: CM
authors.lastname: Medina
authors.forename: Mark
authors.initials: M
authors.lastname: Williams
authors.forename: John M
authors.initials: JM
authors.lastname: Mariadason
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Richard N
authors.initials: RN
authors.lastname: Kitsis
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009124:Muscle Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D009124:Muscle Proteins; C112246:NOL3 protein, human