Abstract
BackgroundWe have preliminarily reported MTA2 expression in gastric cancer and its biological functions by using knockdown cell models, while the molecular mechanisms of MTA2 in regulating malignant behaviors are still unclear.MethodsMTA2 overexpression models were established by transfection assay in gastric cancer cells BGC-823 and MKN28. Cell proliferation assay, colony formation in soft agar, wound-healing assay and transwell migration assay were performed with MTA2 overexpression and negative control (NC) cells. Subcutaneous xenografts and pulmonary metastasis models by BGC-823/MTA2 and BGC-823/NC cells were used to observe the capacity of growth and metastasis in vivo. Differential gene expression in MTA2 knockdown and overexpression cells was analyzed by microarrays. IL-11, which demonstrated as differential expression in microarray, was detected by real-time PCR, western blot, ELISA and immunohistochemistry staining. Recombinant human IL-11 (rhIL-11) was administrated in cell proliferation and colony formation as rescue assay.ResultsThe numbers of colonies in soft agar were significantly more in BGC-823/MTA2 and MKN28/MTA2 cells, comparing with those in their NC cells. Capabilities of cell proliferation, wound-healing and cell migration were not significantly changed in MTA2 overexpression cells. The sizes of subcutaneous xenografts and pulmonary metastases of BGC-832/MTA2 cells were significantly larger than those in BGC-823/NC group. Differential expression of IL-11 was identified by genome expression microarray both in MTA2 knockdown and overexpression cells. IL-11 expression was elevated in BGC-823/MTA2 cells, whereas reduced in SGC-7901/shMTA2 cells. Administration of rhIL-11 recovered colony formation capacity of SGC-7901/shMTA2 cells.ConclusionsMTA2 overexpression enhances colony formation and tumor growth of gastric cancer cells, but not plays important role in cancer cell migration and metastasis. IL-11 is one of the downstream effectors of MTA2 in regulating gastric cancer cells growth.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1366-y) contains supplementary material, which is available to authorized users.
Highlights
We have preliminarily reported Metastasis associated family (MTA2) expression in gastric cancer and its biological functions by using knockdown cell models, while the molecular mechanisms of MTA2 in regulating malignant behaviors are still unclear
MTA2 overexpression promoted cell colony formation in soft agar Introduction of MTA2 into BGC-823 and MKN28 cells was confirmed by both real-time PCR and western blot (Figure 1A)
In soft agar colony formation assay, more colonies were observed in MTA2 overexpression cells (MTA2 vs. negative control (NC), BGC823: 15.8 ± 2.4 vs. 9.0 ± 1.2, P = 0.002; MKN28: 21.0 ± 1.8 vs. 14.3 ± 1.0, P = 0.001, Figure 2B)
Summary
We have preliminarily reported MTA2 expression in gastric cancer and its biological functions by using knockdown cell models, while the molecular mechanisms of MTA2 in regulating malignant behaviors are still unclear. Gastric cancer is one of the most malignant gastrointestinal neoplasms in the world [1]. To improve the outcome of gastric cancer patients, mechanisms of tumorigenesis and progression are under investigation, and intent to clinical translation. Like MTA1, aberrant expression of MTA2 has been reported in several tumors, including ovarian, lung and pancreatic cancer [5,6,7]. We have previously reported that MTA2 gene was overexpressed in gastric cancer tissues, correlating with tumor invasion, lymph node metastasis, and advanced TNM stage. MTA2 knockdown significantly inhibited gastric cancer cell invasion and metastasis [8].
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