title: Protein kinase C ζ regulates survivin expression and inhibits apoptosis in colon cancer.
abstract: The phosphatidylinositol 3-kinase pathway transduces cell survival signals in different malignancies. Protein kinase C ζ (PKCζ) is one of the molecules involved in this pathway. In this study, we investigated the role of PKCζ in apoptosis. Short interfering RNA against PKCζ (siPKCζ) sensitized HCT116 and SW480 colon cancer cells to TRAIL‑induced apoptosis. Among anti-apoptotic proteins, survivin protein and mRNA expression levels decreased after siPKCζ transfection while protein half-life did not change. The expression levels of survivin and PKCζ were correlated in 18 colon cancer specimens (r=0.72, P=3.01x10‑4). Chemosensitivity to 5-FU was enhanced by siPKCζ in HCT116 and SW480 cells. These results indicate that PKCζ regulates survivin expression levels and inhibits apoptosis in colon cancer cells. This study provides a rationale for targeting PKCζ in combination with chemotherapy for colon cancer treatment.
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Umemori
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Kageaki
authors.initials: K
authors.lastname: Kuribayashi
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nirasawa
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondoh
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D000077022:Survivin; D000099221:Protein Kinase C zeta
chemical_list: D005472:Fluorouracil; D051034:Inhibitor of Apoptosis Proteins; D011493:Protein Kinase C; D034741:RNA, Small Interfering; D000077022:Survivin; D000099221:Protein Kinase C zeta; C107489:BIRC5 protein, human