Regulation by heat shock protein 22 (HSPB8) of transforming growth factor-α-induced ovary cancer cell migration.
Accumulating evidence suggests that heat shock proteins (HSPs) are implicated in progression of cancer. HSP22 (HSPB8), a small HSP, is recognized to be ubiquitously expressed in various tissues. However, the expression and the role of HSP22 in ovarian cancer remain to be clarified. In the present study, we investigated the involvement of HSP22 in transforming growth factor (TGF)-α-induced migration of ovarian cancer cells. The expression of HSP22 was detected in a serous ovarian cancer cell line, SKOV3.ip1. The migration was reduced by down-regulation of HSP22 expression. The TGF-α-induced migration was reduced by SB203580 (a p38 MAP kinase inhibitor), SP600125 (a SAPK/JNK inhibitor) and Y27632 (a Rho-kinase inhibitor). However, down-regulation of HSP22 had little effect on the TGF-α-induced phosphorylation of p38 MAP kinase, SAPK/JNK and MYPT, a target protein of Rho-kinase. The HSP22 expression was further analyzed in 20 resected specimens of human ovarian serous carcinoma. The expression of HSP22 was detected in all the twenty tissues (8.24-109.22 pg/mg protein), and the cases with highly expression of HSP22 showed a tendency to acquire the progressive ability. Our results strongly suggest that HSP22 acts as a positive regulator in TGF-α-induced migration of ovarian cancer cells, subsequently directing ovarian cancer toward progression.
Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Mariko
M
Suzuki
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Rie
R
Matsushima-Nishiwaki
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Gen
G
Kuroyanagi
Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Noriko
N
Suzuki
Department of Pathology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Reika
R
Takamatsu
Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Tatsuro
T
Furui
Department of Pathology and Oncology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Naoki
N
Yoshimi
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. Electronic address: okozawa@gifu-u.ac.jp.
Osamu
O
Kozawa
Department of Obstetrics and Gynecology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Ken-ichirou
K
Morishige
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D018832:Molecular Chaperones; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D016211:Transforming Growth Factor alpha; D017346:Protein Serine-Threonine Kinases
HSP22; Migration; Ovary cancer; TGF-α