title: Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis.
abstract: The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras (LA1) mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Hong
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: Somin
authors.initials: S
authors.lastname: Lee
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Lee
authors.forename: Hwi Won
authors.initials: HW
authors.lastname: Seo
authors.forename: Chanhee
authors.initials: C
authors.lastname: Chae
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000235:genetics*
chemical_list: D000336:Aerosols; D017931:DNA Primers; D034741:RNA, Small Interfering; C493558:Slc34a2 protein, mouse; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb