Collectively, the present results demonstrated that miR‑584 inhibited the development of pancreatic cancer by directly targeting CCND1, suggesting that this miRNA may represent a potential therapeutic target for this fatal disease.
Cyclin D1 (CCND1), v‑akt murine thymoma viral oncogene homolog 2 (AKT2), cyclin‑dependent kinase 6 (CDK6) and SMAD family member 2 (SMAD2) were involved in the pathway of pancreatic cancer.
These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.
Our results confirmed that cyclin D1 plays an important role in the growth of pancreatic cancer cells and may be an attractive molecular target for the treatment of human pancreatic cancer.
Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1.
These in vitro characteristics translated to increased tumor growth in both subcutaneous and orthotopic pancreatic cancer murine models and also led to increased liver metastasis. mTrop2 expression also increased the levels of phosphorylated ERK1/2 mediating cell cycle progression by increasing the levels of cyclin D1 and cyclin E as well as downregulating p27.
Aspirin inhibits GSK-3beta activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer.
These data demonstrate that overexpression of p21(WAF1/CIP1) occurs early in the development of PanIN, before aberrations in p53, cyclin D1, and DPC4/Smad4 expression. p21(WAF1/CIP1) overexpression, independent of p53 and/or DPC4/Smad4 expression, may reflect increased Ras activity, either directly through activating K-ras mutations or as a consequence of HER-2/neu (ERBB2) overexpression, both of which are common in PC and in early events in the development of PanIN.
These immunochemical and molecular analyses of the RB1 tumor suppressor gene and cyclin D1 proto-oncogene in a large series of human pancreatic cancers and cell lines indicate that RB1 and cyclin D1 alterations occur during the development of some human DPCAs.