Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer.
Although the morbidity of canine prostate cancer is low, the majority of cases present with resistance to androgen therapy and poor clinical outcomes. These pathological conditions are similar to the signs of the terminal stage of human androgen-independent prostate cancer. The co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) is known to be overexpressed in human androgen-independent prostate cancer. However, there is little information about the structure and function of canine SGTA. In this study, canine SGTA was cloned and analysed for its ability to suppress androgen receptor signalling. The full-length open reading frame (ORF) of the canine SGTA gene was amplified by RT-PCR using primers designed from canine-expressed sequence tags that were homologous to human SGTA. The canine SGTA ORF has high homology with the corresponding human (89%) and mouse (81%) sequences. SGTA dimerisation region and tetratricopeptide repeat (TPR) domains are conserved across the three species. The ability of canine SGTA to undergo homodimerisation was demonstrated by a mammalian two-hybrid system and a pull-down assay. The negative impact of canine SGTA on androgen receptor (AR) signalling was demonstrated using a reporter assay in androgen-independent human prostate cancer cell lines. Pathological analysis showed overexpression of SGTA in canine prostate cancer, but not in hyperplasia. A reporter assay in prostate cells demonstrated suppression of AR signalling by canine SGTA. Altogether, these results suggest that canine SGTA may play an important role in the acquisition of androgen independence by canine prostate cancer cells.
Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Yuiko
Y
Kato
Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan. Electronic address: kochiai@nvlu.ac.jp.
Kazuhiko
K
Ochiai
Department of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Masaki
M
Michishita
Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Daigo
D
Azakami
Department of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Rei
R
Nakahira
Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Masami
M
Morimatsu
Department of Biological Resources, Integrated Center for Science, Ehime University, Ehime 791-0295, Japan.
Toshina
T
Ishiguro-Oonuma
Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, 10 Aomori 034-8628, Japan.
Yasunaga
Y
Yoshikawa
Department of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Masato
M
Kobayashi
Department of Veterinary Clinical Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Makoto
M
Bonkobara
Department of Reproduction, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Masanori
M
Kobayashi
Department of Veterinary Pathology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Kimimasa
K
Takahashi
Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
Masami
M
Watanabe
Department of Veterinary Nursing and Technology, School of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo 180-8602, Japan.
Toshinori
T
Omi
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016366:Open Reading Frames; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000662:veterinary*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D018076:DNA, Complementary; D011944:Receptors, Androgen
Androgen receptor; Cancer; Canine; Prostate; SGTA