Expression and Role of HMGA1 in Renal Cell Carcinoma

被引：34
作者：
Takaha, Natsuki [1 ,2 ]
Sowa, Yoshihiro [3 ]
Takeuchi, Ichiro
Hongo, Fumiya
Kawauchi, Akihiro
Miki, Tsuneharu
机构：
[1] Kyoto Prefectural Univ Med, Dept Translat Canc Drug Dev, Kamigyo Ku, Kyoto 6028566, Japan
[2] Kyoto Prefectural Univ Med, Dept Urol, Kamigyo Ku, Kyoto 6028566, Japan
[3] Kyoto Prefectural Univ Med, Dept Mol Targeting Canc Prevent, Kyoto 6028566, Japan
来源：
JOURNAL OF UROLOGY | 2012年 / 187卷 / 06期
关键词：
apoptosis; carcinoma; renal cell; HMGA1; protein; molecular targeted therapy; anoikis; GROUP PROTEIN I(Y); IN-SITU HYBRIDIZATION; PROSTATE-CANCER CELLS; PANCREATIC ADENOCARCINOMA; ANOIKIS RESISTANCE; DIAGNOSTIC MARKER; GENE-EXPRESSION; TRANSGENIC MICE; GROWTH; METASTASIS;
D O I：
10.1016/j.juro.2012.01.069
中图分类号：
R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
1002 ; 100201 ;
摘要：
Purpose: Although molecular targeted therapy has improved the clinical outcome of metastatic renal cell carcinoma, a complete response is rare and there are various side effects. Identifying novel target molecules is necessary to improve the clinical outcome of metastatic renal cell carcinoma. HMGA1 is over expressed in many types of cancer and it is associated with metastatic potential. It is expressed at low levels or not expressed in normal tissue. We examined HMGA1 expression and function in human renal cell carcinoma. Materials and Methods: HMGA1 expression in surgical specimen from patients with renal cell carcinoma was examined by immunoblot. HMGA1 expression in 6 human renal cell carcinoma cell lines was examined by immunoblot and immunofluorescence. The molecular effects of siRNA mediated knockdown of HMGA1 were examined in ACHN and Caki-1 cells. Results: Immunoblot using surgical specimen showed that HMGA1 was not expressed in normal kidney tissue but it was expressed in tumor tissue in 1 of 30 nonmetastatic (3%) and 6 of 18 metastatic (33%) cases (p = 0.008). Immunoblot and immunofluorescence revealed significant nuclear expression of HMGA1 in ACHN and Caki-1 cells derived from metastatic sites. HMGA1 knockdown remarkably suppressed colony formation and induced significant apoptosis in ACHN and Caki-1 cells. HMGA1 knockdown significantly inhibited invasion and migration in vitro, and induced anoikis associated with P-Akt down-regulation in ACHN cells. Conclusions: HMGA1 is a potential target for novel therapeutic modalities for metastatic renal cell carcinoma.
引用
收藏
页码：2215 / 2222
页数：8
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