Access the full text.
Sign up today, get DeepDyve free for 14 days.
M. Magliano, M. Hebrok (2003)
Hedgehog signalling in cancer formation and maintenanceNature Reviews Cancer, 3
S. Thayer, M. Magliano, P. Heiser, Corinne Nielsen, D. Roberts, G. Lauwers, Y. Qi, Stephan Gysin, C. Castillo, V. Yajnik, B. Antoniu, M. McMahon, A. Warshaw, M. Hebrok (2003)
Hedgehog is an early and late mediator of pancreatic cancer tumorigenesisNature, 425
M. Athar, Chengxin Li, Xiuwei Tang, Sumin Chi, Xiao-li Zhang, A. Kim, S. Tyring, L. Kopelovich, Jennifer Hebert, E. Epstein, D. Bickers, Jingwu Xie (2004)
Inhibition of Smoothened Signaling Prevents Ultraviolet B-Induced Basal Cell Carcinomas through Regulation of Fas Expression and ApoptosisCancer Research, 64
Jingwu Xie, M. Aszterbaum, Xiao-li Zhang, J. Bonifas, C. Zachary, E. Epstein, F. McCormick (2001)
A role of PDGFRα in basal cell carcinoma proliferationProceedings of the National Academy of Sciences of the United States of America, 98
Chengxin Li, Sumin Chi, N. He, Xiao-li Zhang, O. Guicherit, R. Wagner, S. Tyring, Jingwu Xie (2004)
IFNα induces Fas expression and apoptosis in hedgehog pathway activated BCC cells through inhibiting Ras-Erk signalingOncogene, 23
Jingwu Xie, Ronald Johnson, Xiaoli Zhang, J. Bare, F. Waldman, P. Cogen, A. Menon, R. Warren, Ling Chen, Matthew Scott, E. Epstein (1997)
Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors.Cancer research, 57 12
P. Pisani, D. Parkin, F. Bray, J. Ferlay (1999)
Erratum: Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer, 83, 18–29 (1999).International Journal of Cancer, 83
D. Berman, S. Karhadkar, A. Hallahan, J. Pritchard, C. Eberhart, D. Watkins, James Chen, M. Cooper, J. Taipale, J. Olson, P. Beachy (2002)
Medulloblastoma Growth Inhibition by Hedgehog Pathway BlockadeScience, 297
P. Walsh (2005)
Hedgehog signalling in prostate regeneration, neoplasia and metastasis.The Journal of urology, 173 4
Jingwu Xie, M. Murone, S. Luoh, A. Ryan, Q. Gu, Chaohui Zhang, J. Bonifas, C. Lam, M. Hynes, A. Goddard, A. Rosenthal, E. Epstein, F. Sauvage (1998)
Activating Smoothened mutations in sporadic basal-cell carcinomaNature, 391
H. Hahn, C. Wicking, P. Zaphiropoulos, M. Gailani, S. Shanley, A. Chidambaram, I. Vořechovský, E. Holmberg, A. Undén, S. Gillies, K. Negus, I. Smyth, C. Pressman, D. Leffell, B. Gerrard, A. Goldstein, M. Dean, R. Toftgård, G. Chenevix-Trench, B. Wainwright, A. Bale (1996)
Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma SyndromeCell, 85
J. Xie, M. Aszterbaum, X. Zhang, J. Bonifas, C. Zachary, E. Epstein, F. McCormick (2001)
A role of PDGFRalpha in basal cell carcinoma proliferation.Proceedings of the National Academy of Sciences of the United States of America, 98 16
David Berman, Sunil Karhadkar, A. Maitra, Rocio Oca, M. Gerstenblith, K. Briggs, Antony Parker, Y. Shimada, James Eshleman, D. Watkins, P. Beachy (2003)
Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumoursNature, 425
Tao Sheng, Chengxin Li, Xiao-li Zhang, Sumin Chi, N. He, Kai Chen, F. McCormick, Z. Gatalica, Jingwu Xie (2004)
Activation of the hedgehog pathway in advanced prostate cancerMolecular Cancer, 3
D. Watkins, D. Berman, Scott Burkholder, Baolin Wang, P. Beachy, S. Baylin (2003)
Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancerNature, 422
Lian-Ming Fan, Carmen Pepicelli, Christian Dibble, Winnie Catbagan, Jodi Zarycki, Robert Laciak, J. Gipp, Aubie Shaw, M. Lamm, A. Muñoz, R. Lipinski, J. Thrasher, W. Bushman (2004)
Hedgehog signaling promotes prostate xenograft tumor growth.Endocrinology, 145 8
G. Brink, J. Hardwick, Corinne Nielsen, Cui-ping Xu, F. Kate, J. Glickman, S. Deventer, D. Roberts, M. Peppelenbosch (2003)
Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tractMolecular Pathology, 56
F. Borchard (1990)
Classification of gastric carcinoma.Hepato-gastroenterology, 37 2
P. Pisani, D. Parkin, F. Bray, J. Ferlay (1999)
Estimates of the worldwide mortality from 25 cancers in 1990International Journal of Cancer, 83
P. Sánchez, A. Hernández, B. Stecca, Andrea Kahler, Amy Degueme, A. Barrett, Mercedes Beyna, M. Datta, S. Datta, A. Altaba (2004)
Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling.Proceedings of the National Academy of Sciences of the United States of America, 101 34
A. Undén, P. Zaphiropoulos, K. Bruce, R. Toftgård, M. Ståhle-Bäckdahl (1997)
Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma.Cancer research, 57 12
J. Taipale, P. Beachy (2001)
The Hedgehog and Wnt signalling pathways in cancerNature, 411
Ronald Johnson, Alana Rothman, Jingwu Xie, L. Goodrich, J. Bare, J. Bonifas, A. Quinn, R. Myers, David Cox, E. Epstein, M. Scott (1996)
Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus SyndromeScience, 272
The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.
Carcinogenesis – Oxford University Press
Published: Oct 19, 2005
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.