title: Anti-apoptotic effects of PCP4/PEP19 in human breast cancer cell lines: a novel oncotarget.
abstract: The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-Akt(Thr308), enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-Akt(Thr308) and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression.
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Souda
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Sasaguri
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Hatanaka
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tasaki
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Ohi
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.affiliation: Division of Organ Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Umekita
authors.affiliation: Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014162:Transfection
chemical_list: D009419:Nerve Tissue Proteins; C050394:PCP4 protein, human