title: Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation.
abstract: The Family with sequence similarity 107 (FAM107) possesses an N-terminal domain of unknown function (DUF1151) that is highly conserved beyond species. In human, FAM107A termed TU3A/DRR1 has been reported as a candidate tumor suppressor gene which expression is downregulated in several types of cancer, however no studies have investigated the other family protein, FAM107B. In the present study, we designated FAM107B as heat shock-inducible tumor small protein (HITS) and studied its expression and functional properties in cancer. HITS is an 18-kDa nuclear protein expressed in a variety of tissues including stomach, colon, lung and lymphoid organs. In human gastric and colorectal cancers and a mouse model of colon cancer, its expression in tumor cells was much lower than normal epithelial cells, while expression pattern and intensity varied among different histological types of cancer. In functional analysis in vitro, forced expression of this protein suppresses the cellular responses to growth factors. Furthermore, HITS gene carries the promoter region providing heat shock transcription factor (HSF) binding sites and amplifying the transcription of HITS by heat shock or hyperthermia treatment both in vitro and in vivo. Thus HITS would be a potential tumor suppressor gene similar to TU3A containing heat responding elements, which contrasts with previously described oncogenic activities of other heat shock proteins such as HSP70 and HSP90.
authors.affiliation: Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan. hideonak@kanazawa-med.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakajima
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Xia
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Yoshitake
authors.forename: Hideto
authors.initials: H
authors.lastname: Yonekura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nojima
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Takata
authors.forename: Takeo
authors.initials: T
authors.lastname: Shimasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Itaru
authors.initials: I
authors.lastname: Sato
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kawakami
authors.forename: Keita
authors.initials: K
authors.lastname: Koizumi
authors.forename: Toshinari
authors.initials: T
authors.lastname: Minamoto
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Motoo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D006360:Heat-Shock Proteins