Effects of ER-resident and secreted AGR2 on cell proliferation, migration, invasion, and survival in PANC-1 pancreatic cancer cells.

BACKGROUND: Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. METHODS: Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. RESULTS: It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. CONCLUSIONS: Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.

Not every subseptate uterus requires surgical correction to reduce poor reproductive outcome.

OBJECTIVE: To evaluate whether hysteroscopic septoplasty should be performed in all women diagnosed with subseptate uterus. METHODS: In a prospective study, 138 patients diagnosed with subseptate uterus at the First Affiliated Hospital of Guangxi Medical University, Nanning, China, were enrolled between January 1, 2006, and March 1, 2011, and reproductive outcomes were compared among women who did and those who did not undergo hysteroscopic resection. Women were divided in 2 groups: group A comprised women with a history of recurrent spontaneous abortion (RSA), and was subdivided into control (A1) and surgery (A2) groups; group B comprised women with no history of poor reproductive outcomes, and was subdivided into control (B1) and surgery (B2) groups. RESULTS: The rates of pregnancy and term delivery were higher in group A2 than in group A1 (P<0.05). The incidence of RSA and preterm delivery was higher in group A1 than in group A2 (P<0.05). There was no difference in pregnancy rate, incidence of RSA, or preterm or term delivery between group B1 and group B2. CONCLUSION: Hysteroscopic septoplasty significantly improved pregnancy outcomes in women with a history of RSA, but did not influence reproductive outcomes in women with no history of poor pregnancy outcomes.