title: Human selenium binding protein-1 (hSP56) is a negative regulator of HIF-1α and suppresses the malignant characteristics of prostate cancer cells.
abstract: In the present study, we demonstrate that ectopic expression of 56-kDa human selenium binding protein-1 (hSP56) in PC-3 cells that do not normally express hSP56 results in a marked inhibition of cell growth in vitro and in vivo. Down-regulation of hSP56 in LNCaP cells that normally express hSP56 results in enhanced anchorage-independent growth. PC-3 cells expressing hSP56 exhibit a significant reduction of hypoxia inducible protein (HIF)-1α protein levels under hypoxic conditions without altering HIF-1α mRNA (HIF1A) levels. Taken together, our findings strongly suggest that hSP56 plays a critical role in prostate cells by mechanisms including negative regulation of HIF-1α, thus identifying hSP56 as a candidate anti-oncogene product.
authors.affiliation: Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Department of Biochemistry and Cancer Research Institute, Kosin University College of Medicine, Busan 602-703, Korea.
authors.forename: Jee-Yeong
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Zhou
authors.affiliation: Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Gao
authors.affiliation: Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Feldman
authors.affiliation: Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Oncology Therapeutic Area, Quintiles Translational, Arlington, MA 02476,USA.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Sytkowski
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051137:Selenium-Binding Proteins / Q000378:metabolism*; D014183:Transplantation, Heterologous; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; C459591:USP20 protein, human; C449799:USP33 protein, human; D043222:Ubiquitin Thiolesterase