title: Human STEAP3 maintains tumor growth under hypoferric condition.
abstract: Iron is essential in cellular proliferation and survival based on its crucial roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients with low serum iron, although their actual mechanisms are not well known. To elucidate molecular mechanisms of efficient tumor progression under the hypoferric condition, we studied the roles of six-transmembrane epithelial antigen of the prostate family member 3 (STEAP3), which was reported to facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human STEAP3-overexpressing cells were established. The impact of STEAP3 expression was analyzed about the amount of iron storage, the survival under hypoferric conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even in hypoferric mice, while parental Raji cells grew less rapidly. In addition, iron deficiency enhanced STEAP3 mRNA expression in tumor cells. Furthermore, human colorectal cancer tissues exhibited more STEAP3 mRNA expression and iron storage compared with normal colon mucosa. These findings indicate that STEAP3 maintains iron storage in human malignant cells and tumor proliferation under the hypoferric condition.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. tisobe@intmed1.med.kyushu-u.ac.jp
authors.forename: Taichi
authors.initials: T
authors.lastname: Isobe
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.forename: Shuji
authors.initials: S
authors.lastname: Arita
authors.forename: Masato
authors.initials: M
authors.lastname: Komoda
authors.forename: Shingo
authors.initials: S
authors.lastname: Tamura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ariyama
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takaishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusaba
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueki
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D002470:Cell Survival; D005293:Ferritins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D000090463:Iron Deficiencies; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron; D010088:Oxidoreductases; C486677:STEAP3 protein, human