INTRODUCTION: Pancreatic cancer is an aggressive malignancy with a poor prognosis. The overall 5-year survival rate of pancreatic cancer is less than 5%, and has not improved significantly for years. Further understanding of the molecular carcinogenesis of pancreatic cancer is critical for designing effective ways to treat this type of malignancy. METHODS: In this study, we examine expression of hedgehog signaling molecules in 54 surgically removed pancreatic cancer specimens as well as seven available pancreatic cancer cell lines. RESULTS: We find that expression of Ptch is associated with tumor size, tumor differentiation, lymph node metastasis, and clinical stages, whereas expression of Smo is associated with tumor differentiation and lymph node metastasis. Our studies from pancreatic cancer cell lines indicate that targeted inhibition of hedgehog signaling by Smo signaling inhibitor KAAD-cyclopamine causes hedgehog target gene expression (Gli1) suppression, induces P21 expression and G1 cell population, and reduced expression of Cyclin D1 and IGF2. CONCLUSIONS: These results indicate that hedgehog signaling activation is a very common event in pancreatic cancer and that targeted inhibition of hedgehog signaling may be effective in treatment of pancreatic cancer.
INTRODUCTION:Pancreatic cancer is an aggressive malignancy with a poor prognosis. The overall 5-year survival rate of pancreatic cancer is less than 5%, and has not improved significantly for years. Further understanding of the molecular carcinogenesis of pancreatic cancer is critical for designing effective ways to treat this type of malignancy. METHODS: In this study, we examine expression of hedgehog signaling molecules in 54 surgically removed pancreatic cancer specimens as well as seven available pancreatic cancer cell lines. RESULTS: We find that expression of Ptch is associated with tumor size, tumor differentiation, lymph node metastasis, and clinical stages, whereas expression of Smo is associated with tumor differentiation and lymph node metastasis. Our studies from pancreatic cancer cell lines indicate that targeted inhibition of hedgehog signaling by Smo signaling inhibitor KAAD-cyclopamine causes hedgehog target gene expression (Gli1) suppression, induces P21 expression and G1 cell population, and reduced expression of Cyclin D1 and IGF2. CONCLUSIONS: These results indicate that hedgehog signaling activation is a very common event in pancreatic cancer and that targeted inhibition of hedgehog signaling may be effective in treatment of pancreatic cancer.
Authors: Jennifer P Morton; Michelle E Mongeau; David S Klimstra; John P Morris; Yie Chia Lee; Yoshiya Kawaguchi; Christopher V E Wright; Matthias Hebrok; Brian C Lewis Journal: Proc Natl Acad Sci U S A Date: 2007-03-19 Impact factor: 11.205
Authors: Hany Kayed; Jörg Kleeff; Shereen Keleg; Junchau Guo; Knut Ketterer; Pascal O Berberat; Nathalia Giese; Irene Esposito; Thomas Giese; Markus W Büchler; Helmut Friess Journal: Int J Cancer Date: 2004-07-10 Impact factor: 7.396
Authors: David M Berman; Sunil S Karhadkar; Anirban Maitra; Rocio Montes De Oca; Meg R Gerstenblith; Kimberly Briggs; Antony R Parker; Yutaka Shimada; James R Eshleman; D Neil Watkins; Philip A Beachy Journal: Nature Date: 2003-09-14 Impact factor: 49.962
Authors: Kimberly Walter; Noriyuki Omura; Seung-Mo Hong; Margaret Griffith; Audrey Vincent; Michael Borges; Michael Goggins Journal: Clin Cancer Res Date: 2010-03-09 Impact factor: 12.531
Authors: Dongsheng Gu; Hailan Liu; Gloria H Su; Xiaoli Zhang; Helen Chin-Sinex; Helmut Hanenberg; Marc S Mendonca; Harlan E Shannon; E Gabriela Chiorean; Jingwu Xie Journal: Mol Cancer Ther Date: 2013-03-06 Impact factor: 6.261
Authors: Liza E O'Donoghue; Andrey A Ptitsyn; Debra A Kamstock; Janet Siebert; Russell S Thomas; Dawn L Duval Journal: BMC Cancer Date: 2010-09-22 Impact factor: 4.430