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MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.
- Source :
-
Molecular cancer [Mol Cancer] 2013 Sep 08; Vol. 12 (1), pp. 102. Date of Electronic Publication: 2013 Sep 08. - Publication Year :
- 2013
-
Abstract
- Background: MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined.<br />Methods: Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biological function investigation. Binding and regulation activities of Sp1 on MTA2 promoter were investigated by chromatin immunoprecipitation and luciferase reporter gene.<br />Results: The expression rate of MTA2 in gastric cancer tissues was 55.9% (71/127), and its expression was closely related to the depth of tumor invasion, lymph nodes metastasis, and TNM staging. MTA2 knockdown in human SGC-7901 and AGS gastric cancer cells significantly inhibited migration and invasion in vitro, and disrupted structure of cytoskeleton. MTA2 knockdown also attenuated xenografts growth and lung metastasis in nude mice model. MTA2 expression was positively correlated with transcription factor Sp1 in gastric cancer tissues (r = 0.326, P < 0.001). Sp1 bound to human MTA2 gene promoter at region from -1043 bp to -843 bp. Transcriptional activity of MTA2 promoter could be enhanced by Sp1 overexpression.<br />Conclusions: MTA2 knockdown impairs invasion and metastasis of gastric cancer cells, and attenuates xenografts growth in vivo. Sp1 regulates MTA2 expression at transcriptional level.
- Subjects :
- Actin Cytoskeleton metabolism
Adenocarcinoma mortality
Adenocarcinoma secondary
Animals
Binding Sites
Cell Line, Tumor
Cell Movement
Gene Expression Regulation, Neoplastic
Histone Deacetylases metabolism
Humans
Lung Neoplasms metabolism
Lung Neoplasms secondary
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Transplantation
Promoter Regions, Genetic
Repressor Proteins metabolism
Stomach Neoplasms mortality
Stomach Neoplasms pathology
Transcription, Genetic
Adenocarcinoma metabolism
Histone Deacetylases genetics
Lung Neoplasms genetics
Repressor Proteins genetics
Sp1 Transcription Factor physiology
Stomach Neoplasms genetics
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4598
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular cancer
- Publication Type :
- Academic Journal
- Accession number :
- 24010737
- Full Text :
- https://doi.org/10.1186/1476-4598-12-102