Expression and prognostic significance of SIRT1 in ovarian epithelial tumours

被引:116
作者
Jang, Kyu Yun [1 ]
Kim, Kwan Sik [2 ]
Hwang, Sung Ho [1 ]
Kwon, Keun Sang [3 ]
Kim, Kyung Ryoul [1 ]
Park, Ho Sung [1 ]
Park, Byung-Hyun [4 ]
Chung, Myoung Ja [1 ]
Kang, Myoung Jae [1 ]
Lee, Dong Geun [1 ]
Moon, Woo Sung [1 ]
机构
[1] Chonbuk Natl Univ, Dept Pathol, Sch Med, Dept Pathol, Jeonju 561180, Jeonbuk, South Korea
[2] Chonbuk Natl Univ, Sch Med, Dept Obstet & Gynecol, Jeonju 561180, Jeonbuk, South Korea
[3] Chonbuk Natl Univ, Sch Med, Dept Prevent Med, Jeonju 561180, Jeonbuk, South Korea
[4] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju 561180, Jeonbuk, South Korea
关键词
Ovary; epithelial tumours; prognosis; SIRT1; p53; CELL-SURVIVAL; P53; PROTEIN; DEACETYLASE; CARCINOMA; CANCER; TRANSCRIPTION; SUPPRESSOR;
D O I
10.1080/00313020902884451
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Aims: Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, some studies have suggested that SIRT1 could be over-expressed in breast, prostate and colon cancers and up-regulated SIRT1 inactivates p53 by deacetylation. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 and p53 expression in ovarian epithelial tumours. Methods: Immunohistochemical expression of SIRT1 and p53 were evaluated using tissue microarray in 40 cases of benign epithelial tumours, 36 cases of borderline tumours, and 90 cases of malignant tumours. Results: Expression of SIRT1 was significantly increased in malignant epithelial tumours compared to benign and borderline epithelial tumours (p0.001). In particular, a high proportion of serous carcinoma expressed SIRT1 (86%, 55/64 cases). Despite the frequent expression of SIRT1 in malignant ovarian epithelial tumours, serous carcinomas of high FIGO stage showed less frequent SIRT1 expression compared to that of low stage serous carcinomas (p=0.029). Moreover, increased expression of SIRT1 in serous carcinoma correlated with increased overall survival by univariate (p=0.014) and multivariate analyses. Conclusions: Over-expression of SIRT1 may play an important role in the early stage of ovarian carcinogenesis.
引用
收藏
页码:366 / 371
页数:6
相关论文
共 23 条
[1]   Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? [J].
Baylin, SB ;
Ohm, JE .
NATURE REVIEWS CANCER, 2006, 6 (02) :107-116
[2]   The Sir2 family of protein deacetylases [J].
Blander, G ;
Guarente, L .
ANNUAL REVIEW OF BIOCHEMISTRY, 2004, 73 :417-435
[3]   Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase [J].
Brunet, A ;
Sweeney, LB ;
Sturgill, JF ;
Chua, KF ;
Greer, PL ;
Lin, YX ;
Tran, H ;
Ross, SE ;
Mostoslavsky, R ;
Cohen, HY ;
Hu, LS ;
Cheng, HL ;
Jedrychowski, MP ;
Gygi, SP ;
Sinclair, DA ;
Alt, FW ;
Greenberg, ME .
SCIENCE, 2004, 303 (5666) :2011-2015
[4]   Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses [J].
Chen, WY ;
Wang, DH ;
Yen, RWC ;
Luo, JY ;
Gu, W ;
Baylin, SB .
CELL, 2005, 123 (03) :437-448
[5]   Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis [J].
Cohen, HY ;
Lavu, S ;
Bitterman, KJ ;
Hekking, B ;
Imahiyerobo, TA ;
Miller, C ;
Frye, R ;
Ploegh, H ;
Kessler, BM ;
Sinclair, DA .
MOLECULAR CELL, 2004, 13 (05) :627-638
[6]   Quantification of p53 in epithelial ovarian cancer [J].
Geisler, JP ;
Geisler, HE ;
Wiemann, MC ;
Givens, SS ;
Zhou, Z ;
Miller, GA .
GYNECOLOGIC ONCOLOGY, 1997, 66 (03) :435-438
[7]   Strong expression of a longevity-related protein, SIRT1, in Bowen's disease [J].
Hida, Yasutoshi ;
Kubo, Yoshiaki ;
Murao, Kazutoshi ;
Arase, Seiji .
ARCHIVES OF DERMATOLOGICAL RESEARCH, 2007, 299 (02) :103-106
[8]   Microinvasion links ovarian serous borderline tumor and grade 1 invasive carcinoma [J].
Hogg, Russell ;
Scurry, James ;
Kim, Soo-Nyung ;
Friedlander, Michael ;
Hacker, Neville .
GYNECOLOGIC ONCOLOGY, 2007, 106 (01) :44-51
[9]   SIRT1 is significantly elevated in mouse and human prostate cancer [J].
Huffman, Derek M. ;
Grizzle, William E. ;
Bamman, Marcas M. ;
Kim, Jeong-su ;
Eltoum, Isam A. ;
Elgavish, Ada ;
Nagy, Tim R. .
CANCER RESEARCH, 2007, 67 (14) :6612-6618
[10]   Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase [J].
Imai, S ;
Armstrong, CM ;
Kaeberlein, M ;
Guarente, L .
NATURE, 2000, 403 (6771) :795-800