MTA2 enhances colony formation and tumor growth of gastric cancer cells through IL-11.
BACKGROUND
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.


METHODS
MTA2 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.


RESULTS
The 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.


CONCLUSIONS
MTA2 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.
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. zhou_chenfei@126.com.
Chenfei
C
Zhou
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. jj40464@126.com.
Jun
J
Ji
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. qu_cai@126.com.
Qu
Q
Cai
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. shimin0412005@126.com.
Min
M
Shi
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. xuehua_chenxh@126.com.
Xuehua
X
Chen
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. yingyan3y@126.com.
Yingyan
Y
Yu
Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. drzzg1954@163.com.|Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. drzzg1954@163.com.
Zhenggang
Z
Zhu
Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China. jun_zj10977@163.com.
Jun
J
Zhang
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
C508611:IL11 protein, human; D017370:Interleukin-11; D012097:Repressor Proteins; C120917:MTA2 protein, human; D006655:Histone Deacetylases