Induction of HITS, a newly identified family with sequence similarity 107 protein (FAM107B), in cancer cells by heat shock stimulation.
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.
Nakajima
Hideo
H
Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan. hideonak@kanazawa-med.ac.jp
Ishigaki
Yasuhito
Y
Xia
Qi-Sheng
QS
Ikeda
Takayuki
T
Yoshitake
Yoshino
Y
Yonekura
Hideto
H
Nojima
Takayuki
T
Tanaka
Takuji
T
Umehara
Hisanori
H
Tomosugi
Naohisa
N
Takata
Takanobu
T
Shimasaki
Takeo
T
Nakaya
Naoki
N
Sato
Itaru
I
Kawakami
Kazuyuki
K
Koizumi
Keita
K
Minamoto
Toshinari
T
Motoo
Yoshiharu
Y
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
D006360:Heat-Shock Proteins