Non-Genomic Estrogen/Estrogen Receptor α Promotes Cellular Malignancy of Immature Ovarian Teratoma In Vitro

被引:17
作者
Hung, Yao-Ching [1 ,2 ,3 ]
Chang, Wei-Chun [1 ,2 ,3 ]
Chen, Lu-Min [1 ,2 ,3 ]
Chang, Ying-Yi [1 ,2 ,4 ]
Wu, Ling-Yu [1 ,2 ]
Chung, Wei-Min [1 ,2 ,3 ]
Lin, Tze-Yi [1 ,2 ]
Chen, Liang-Chi [1 ,2 ]
Ma, Wen-Lung [1 ,2 ,3 ]
机构
[1] China Med Univ Hosp, Dept Obstet & Gynecol, Sex Hormone Res Ctr, Taichung 404, Taiwan
[2] China Med Univ Hosp, Dept Pathol, Taichung 404, Taiwan
[3] China Med Univ, Grad Inst Clin Med Sci, Sch Med, Taichung, Taiwan
[4] China Med Univ, Grad Inst Publ Hlth Sci, Sch Publ Hlth, Taichung, Taiwan
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; ANDROGEN RECEPTOR; FOCAL ADHESION; CANCER; ESTROGEN; ACTIVATION; PATHWAY; KINASE; CELLS; IDENTIFICATION;
D O I
10.1002/jcp.24495
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Malignant immature ovarian teratomas (IOTs) most often occur in women of reproductive age. It is unclear, however, what roles estrogenic signaling plays in the development of IOT. In this study, we examined whether estrogen receptors (ER and ) promote the cellular malignancy of IOT. Estradiol (E2), PPT (propylpyrazole), and DPN (diarylpropionitrile) (ER- and -specific agonists, respectively), as well as ER- or ER-specific short hairpin (sh)RNA were applied to PA-1 cells, a well-characterized IOT cell line. Cellular tumorigenic characteristics, for example, cell migration/invasion, expression of the cancer stem/progenitor cell marker CD133, and evidence for epithelial-mesenchymal transition (EMT) were examined. In PA-1 cells that expressed ER and ER, we found that ER promoted cell migration and invasion. We also found that E2/ER signaling altered cell behavior through non-classical transactivation function. Our data show non-genomic E2/ER activations of focal adhesion kinase-Ras homolog gene family member A (FAK-RhoA) and ERK governed cell mobility capacity. Moreover, E2/ER signaling induces EMT and overexpression of CD133 through upregulation micro-RNA 21 (miR21; IOT stem/progenitor promoter), and ERK phosphorylations. Furthermore, E2/ER signaling triggers a positive feedback regulatory loop within miR21 and ERK. At last, expression levels of ER, CD133, and EMT markers in IOT tissue samples were examined by immunohistochemistry. We found that cytosolic ER was co-expressed with CD133 and mesenchymal cell markers but not epithelial cell markers. In conclusion, estrogenic signals exert malignant transformation capacity of cancer cells, exclusively through non-genomic regulation in female germ cell tumors. J. Cell. Physiol. 229: 752-761, 2014. (c) 2013 Wiley Periodicals, Inc.
引用
收藏
页码:752 / 761
页数:10
相关论文
共 47 条
  • [1] Epithelial Mesenchymal Transition and Cancer Stem Cell-Like Phenotypes Facilitate Chemoresistance in Recurrent Ovarian Cancer
    Ahmed, N.
    Abubaker, K.
    Findlay, J.
    Quinn, M.
    [J]. CURRENT CANCER DRUG TARGETS, 2010, 10 (03) : 268 - 278
  • [2] miR-21 Promotes Fibrogenic Epithelial-to-Mesenchymal Transition of Epicardial Mesothelial Cells Involving Programmed Cell Death 4 and Sprouty-1
    Bronnum, Hasse
    Andersen, Ditte C.
    Schneider, Mikael
    Sandberg, Maria B.
    Eskildsen, Tilde
    Nielsen, Solveig B.
    Kalluri, Raghu
    Sheikh, Soren P.
    [J]. PLOS ONE, 2013, 8 (02):
  • [3] Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion
    Carragher, NO
    Frame, MC
    [J]. TRENDS IN CELL BIOLOGY, 2004, 14 (05) : 241 - 249
  • [4] Glyoxalase-I Is a Novel Prognosis Factor Associated with Gastric Cancer Progression
    Cheng, Wan-Li
    Tsai, Ming-Ming
    Tsai, Chung-Ying
    Huang, Ya-Hui
    Chen, Cheng-Yi
    Chi, Hsiang-Cheng
    Tseng, Yi-Hsin
    Chao, Im-Wai
    Lin, Wei-Chi
    Wu, Sheng-Ming
    Liang, Ying
    Liao, Chia-Jung
    Lin, Yang-Hsiang
    Chung, I-Hsiao
    Chen, Wei-Jan
    Lin, Paul Y.
    Wang, Chia-Siu
    Lin, Kwang-Huei
    [J]. PLOS ONE, 2012, 7 (03):
  • [5] MicroRNA-21 promotes the ovarian teratocarcinoma PA1 cell line by sustaining cancer stem/progenitor populations in vitro
    Chung, Wei-Min
    Chang, Wei-Chun
    Chen, Lumin
    Chang, Ying-Yi
    Shyr, Chih-Rong
    Hung, Yao-Ching
    Ma, Wen-Lung
    [J]. STEM CELL RESEARCH & THERAPY, 2013, 4
  • [6] Regulatory networks defining EMT during cancer initiation and progression
    De Craene, Bram
    Berx, Geert
    [J]. NATURE REVIEWS CANCER, 2013, 13 (02) : 97 - 110
  • [7] PReMod:: a database of genome-wide mammalian cis-regulatory module predictions
    Ferretti, Vincent
    Poitras, Christian
    Bergeron, Dominique
    Coulombe, Benoit
    Robert, Francois
    Blanchette, Mathieu
    [J]. NUCLEIC ACIDS RESEARCH, 2007, 35 : D122 - D126
  • [8] RAPID AND LONG-TERM EFFECTS OF 17-BETA-ESTRADIOL ON PIP2-PHOSPHOLIPASE C-SPECIFIC ACTIVITY OF MCF-7 CELLS
    GRABER, R
    SUMIDA, C
    VALLETTE, G
    NUNEZ, EA
    [J]. CELLULAR SIGNALLING, 1993, 5 (02) : 181 - 186
  • [9] Hammond MEH, 2010, ARCH PATHOL LAB MED, V134, pE48, DOI 10.1043/1543-2165-134.7.e48
  • [10] Hollenhorst Peter C, 2012, Small GTPases, V3, P154, DOI 10.4161/sgtp.19630