Open AccessREG4 contributes to the invasiveness of pancreatic cancer by upregulating MMP‐7 and MMP‐9
Author(s) -
He XuJun,
Jiang XiaoTing,
Ma YingYu,
Xia YingJie,
Wang HuiJu,
Guan TianPei,
Shao QinShu,
Tao HouQuan
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12018
Subject(s) - pancreatic cancer , gentamicin protection assay , blot , mtt assay , immunohistochemistry , cancer research , western blot , cancer , cell culture , cell growth , matrix metalloproteinase , downregulation and upregulation , cancer cell , biology , microbiology and biotechnology , medicine , metastasis , pathology , gene , biochemistry , genetics
Recent studies have shown that overexpression of regenerating gene family member 4 ( REG 4 ) is associated with the initiation and progression of pancreatic cancer. In our study, we explored the role of REG 4 in the invasion of pancreatic cancer. Real‐time PCR and Western blot analysis were used to determine REG 4 expression in pancreatic cancer cell lines. An MTT assay was carried out to test the effect of REG 4 on the growth of pancreatic cancer cells. The involvement of REG 4 in cancer cell invasion was examined by Transwell invasion assay. Two MMP s, MMP ‐7 and MMP ‐9 , were identified from a pool of candidate genes as being related to REG 4 ‐induced cell invasion by PCR and Western blotting. Immunohistochemistry was used to confirm the correlation between REG 4 and the two MMP s. High expression of REG 4 was found in BXPC ‐3 cells and its culture media. But in PANC ‐1 and ASPC ‐1 cell lines, REG 4 expression levels were very low, and no detectable protein was found in the culture medium. The MTT and Transwell invasion assays showed that recombinant REG 4 protein and BXPC ‐3 conditioned media significantly promoted the proliferation and invasiveness of pancreatic cancer cells. It was also shown that MMP ‐7 and MMP ‐9 are upregulated by REG 4 induction using real‐time PCR and Western blotting analysis. Immunohistochemical study further verified this result. In conclusion, REG 4 promotes not only growth but also in vitro invasiveness of pancreatic cancer cells by upregulating MMP ‐7 and MMP ‐9.