Linked Life Data

19956873

Source:http://linkedlifedata.com/resource/pubmed/id/19956873

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-3
pubmed:abstractText
Neuroblastoma (NB) is the most common pediatric extracranial cancer. Metastasis is the main cause of mortality in NB patients. Currently, little is known about the risk factors and their mechanisms that cause metastasis. Environmental endocrine disruptors (EED) are recently identified risk factors associated with various human diseases including malignant tumors. Our previous studies have implicated the role of di(2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA), two of the most common EED, in neuroblastoma cell proliferation. Here, we further investigated the effects of DEHP, BPA as well as 17beta-estradiol (E2) on the invasion and metastasis of human neuroblastoma SK-N-SH cells in vitro. SK-N-SH cells expressed estrogen receptor (ER)-beta, matrix metalloproteinases-2 (MMP-2), MMP-9 and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) at readily detectable levels. 50 microM DEHP, 0.1 microM BPA and 10 microM E2 exposure all resulted in enhanced motility and invasiveness of SK-N-SH cells (P<0.001), elevated expression of MMP-2 and MMP-9, and decreased expression of TIMP-2 (P<0.01). Furthermore, phosphorylation of Akt (Ser473) was also induced following the exposure (P<0.01). Importantly, both ER antagonist ICI182,780 and phosphoinositide 3-kinase (PI3K) specific inhibitor LY294002 significantly inhibited the DEHP, BPA, or E2-induced cell migration and invasion, as well as the disregulation of MMP-2, MMP-9 and TIMP-2 expression. ICI182,780 may have worked through abolishing Akt (Ser473) phosphorylation. In conclusion, DEHP, BPA, and E2 potently promote invasion and metastasis of neuroblastoma cells through overexpression of MMP-2 and MMP-9 as well as downregulation of TIMP-2. ER-dependent pathway and PI3K/Akt pathway are involved, which may become potential therapeutic targets for neuroblastoma treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1791-2431
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
129-39
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19956873-Cell Line, Tumor, pubmed-meshheading:19956873-Diethylhexyl Phthalate, pubmed-meshheading:19956873-Endocrine System, pubmed-meshheading:19956873-Estradiol, pubmed-meshheading:19956873-Estrogens, Non-Steroidal, pubmed-meshheading:19956873-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19956873-Humans, pubmed-meshheading:19956873-Matrix Metalloproteinase 2, pubmed-meshheading:19956873-Matrix Metalloproteinase 9, pubmed-meshheading:19956873-Neoplasm Invasiveness, pubmed-meshheading:19956873-Neoplasm Metastasis, pubmed-meshheading:19956873-Neuroblastoma, pubmed-meshheading:19956873-Phenols, pubmed-meshheading:19956873-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19956873-Plasticizers, pubmed-meshheading:19956873-Tissue Inhibitor of Metalloproteinase-2
pubmed:year
2010
pubmed:articleTitle
Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells.
pubmed:affiliation
Department of Surgery, Children's Hospital, Fudan University, Shanghai, P.R. China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't