Expression and regulation of hedgehog signaling pathway in pancreatic cancer.
BACKGROUND
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.
Yang
Yinmo
Y
Department of Surgery, Peking University First Hospital, Beijing, 100034, People's Republic of China. yangyinmo@263.net
Tian
Xiaodong
X
Xie
Xuehai
X
Zhuang
Yan
Y
Wu
Wenhan
W
Wang
Weimin
W
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002934:Cinnamates / Q000494:pharmacology; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014704:Veratrum Alkaloids / Q000494:pharmacology
C542465:3-keto-N-aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine; C493956:CDKN1A protein, human; D002934:Cinnamates; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053823:Hedgehog Proteins; C035170:IGF2 protein, human; D014704:Veratrum Alkaloids; D019938:Cyclin D1; D007335:Insulin-Like Growth Factor II