Gonadotropins and ovarian cancer

被引:133
作者
Choi, Jung-Hye
Wong, Alice S. T.
Huang, He-Feng
Leung, Peter C. K.
机构
[1] Univ British Columbia, Dept Obstet & Gynecol, Child & Family Res Inst, Vancouver, BC V6H 3V5, Canada
[2] Zhejiang Univ, Sch Med, Dept Obstet & Gynecol, Zhejiang 310016, Peoples R China
[3] Univ Hong Kong, Dept Zool, Hong Kong, Hong Kong, Peoples R China
关键词
D O I
10.1210/er.2006-0036
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ovarian epithelial cancer (OEC) accounts for 90% of all ovarian cancers and is the leading cause of death from gynecological cancers in North America and Europe. Despite its clinical significance, the factors that regulate the development and progression of ovarian cancer are among the least understood of all major human malignancies. The two gonadotropins, FSH and LH, are key regulators of ovarian cell functions, and the potential role of gonadotropins in the pathogenesis of ovarian cancer is suggested. Ovarian carcinomas have been found to express specific receptors for gonadotropins. The presence of gonadotropins in ovarian tumor fluid suggests the importance of these factors in the transformation and progression of ovarian cancers as well as being prognostic indicators. Functionally, there is evidence showing a direct action of gonadotropins on ovarian tumor cell growth. This review summarizes the key findings and recent advances in our understanding of these peptide hormones in ovarian cancer development and progression and their role in potential future cancer therapy. We will first discuss the supporting evidence and controversies in the " gonadotropin theory" and the use of animal models for exploring the involvement of gonadotropins in the etiology of ovarian cancer. The role of gonadotropins in regulating the proliferation, survival, and metastasis of OEC is next summarized. Relevant data from ovarian surface epithelium, which is widely believed to be the precursor of OEC, are also described. Finally, we will discuss the clinical applications of gonadotropins in ovarian cancer and the recent progress in drug development.
引用
收藏
页码:440 / 461
页数:22
相关论文
共 260 条
[1]  
ADAMS AT, 1981, CANCER RES, V41, P2063
[2]   Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene [J].
Aittomaki, K ;
Herva, R ;
Stenman, UH ;
Juntunen, K ;
Ylostalo, P ;
Hovatta, O ;
delaChapelle, A .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (10) :3722-3726
[3]   MUTATION IN THE FOLLICLE-STIMULATING-HORMONE RECEPTOR GENE CAUSES HEREDITARY HYPERGONADOTROPIC OVARIAN FAILURE [J].
AITTOMAKI, K ;
LUCENA, JLD ;
PAKARINEN, P ;
SISTONEN, P ;
TAPANAINEN, J ;
GROMOLL, J ;
KASKIKARI, R ;
SANKILA, EM ;
LEHVASLAIHO, H ;
ENGEL, AR ;
NIESCHLAG, E ;
HUHTANIEMI, I ;
DELACHAPELLE, A .
CELL, 1995, 82 (06) :959-968
[4]   Differential expression of progesterone receptor isoforms A and B in the normal ovary, and in benign, borderline, and malignant ovarian tumors [J].
Akahira, J ;
Suzuki, T ;
Ito, K ;
Kaneko, C ;
Darnel, AD ;
Moriya, T ;
Okamura, K ;
Yaegashi, N ;
Sasano, H .
JAPANESE JOURNAL OF CANCER RESEARCH, 2002, 93 (07) :807-815
[5]   Luteinizing hormone, its β-subunit variant, and epithelial ovarian cancer:: The gonadotropin hypothesis revisited [J].
Akhmedkhanov, A ;
Toniolo, P ;
Zeleniuch-Jacquotte, A ;
Pettersson, KS ;
Huhtaniemi, IT .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2001, 154 (01) :43-49
[6]   Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation [J].
Alam, H ;
Maizels, ET ;
Park, Y ;
Ghaey, S ;
Feiger, ZJ ;
Chandel, NS ;
Hunzicker-Dunn, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (19) :19431-19440
[7]  
ALFTHAN H, 1992, CANCER RES, V52, P4628
[8]   CYCLIC-AMP-DEPENDENT ACTIVATION OF RAP1B [J].
ALTSCHULER, DL ;
PETERSON, SN ;
OSTROWSKI, MC ;
LAPETINA, EG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (18) :10373-10376
[9]   Implementation of the Women's Health Initiative Study Design [J].
Anderson, GL ;
Manson, J ;
Wallace, R ;
Lund, B ;
Hall, D ;
Davis, S ;
Shumaker, S ;
Wang, CY ;
Stein, E ;
Prentice, RL .
ANNALS OF EPIDEMIOLOGY, 2003, 13 (09) :S5-S17
[10]  
Anderson S M, 1996, S D J Med, V49, P419