Nek2 as a novel molecular target for the treatment of breast carcinoma.
We investigated the role of Nek2, a member of the serine-threonine kinase family, in the tumorigenic growth of breast carcinoma. Increased expression of Nek2 was observed in all breast carcinoma cell lines examined (BT20, BT474, Hs578T, MCF7, MDA-MB-231, T47D, and ZR-75-1) by immunoblotting. By treatment with Nek2 short interfering RNA (siRNA), expression of Nek2 was clearly decreased in both estrogen receptor (ER)-positive (MCF7) and ER-negative (MDA-MB-231) breast carcinoma cell lines. Cell growth, colony formation in soft agar, and in vitro invasiveness of these cell lines were substantially suppressed by Nek2 siRNA treatment. In a xenograft nude mouse model with subcutaneous implantation of MCF7 or MDA-MB-231, subcutaneous injection of Nek2 siRNA around the tumor nodules resulted in a reduction of tumor size compared with those of control siRNA injection. Taken together, Nek2 appears to play a pivotal role in tumorigenic growth of breast carcinoma cells, and could be a useful therapeutic molecular target for the treatment of breast carcinoma both in ER-positive and ER-negative cases.
Tsunoda
Nobuyuki
N
Division of Surgical Oncology, Nagoya University, Graduate School of Medicine, 65-Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kokuryo
Toshio
T
Oda
Koji
K
Senga
Takeshi
T
Yokoyama
Yukihiro
Y
Nagino
Masato
M
Nimura
Yuji
Y
Hamaguchi
Michinari
M
D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis
D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases