Fragments of the ERBB2 promote act differently in breast and in ovary or colon cancer cells we have analysed. Additional studies are needed to understand the mechanisms responsible http://www.selleckchem.com/products/carfilzomib-pr-171.html for the increased accumulation of the erbB-2 transcript and protein in non-breast cancer cells. Acknowledgments We thank Dr R Kiss for the pancreatic cell lines, Drs J Piette, M Grooteclaes and L Delacroix for critically reading the manuscript. This work was supported by a Grant from the Belgian ��Fonds National pour la Recherche Scientifique (F.N.R.S.)��, ��F��d��ration belge contre le Cancer��, ��Centre Anticanc��reux pr��s l’Universit�� de Li��ge�� and ��Fondation pour promouvoir la Recherche �� l’Ulg��. Rosita Winkler and Philippe Delvenne are Chercheur Qualifi�� du F.N.R.S. Douglas Vernimmen is a recipient of a T��l��vie Grant from the F.

N.R.S.
Cancer of the exocrine pancreas is the fourth leading cause of cancer-related deaths in both men and women (Fernandez et al, 1994). Even if advances in surgical techniques, radiation and chemotherapy have provided significant improvements in the overall survival and on the quality of life, fewer than 5% of pancreatic cancer (PC) patients survive 5 years after diagnosis (Parker et al, 1996). Therefore, it is not surprising that PC is a serious health problem. Thus, there is a great demand for new and more effective therapeutic strategies for the treatment of this disease. Recent studies on pancreatic tumour tissues and cell lines have shown that multiple subsets of genes undergo activation or inactivation during development and progression of disease (Hilgers and Kern, 1999).

Specific point mutations at codon 12 of the K-ras oncogene are detected in 75�C90% of PC specimens and constitute the most common genetic changes in PC (Almoguera et al, 1988). The mutated K-ras protein is not able to convert GTP to GDP, resulting in constitutively active GTP-bound species and constitutive activation of cell proliferative signals. It is therefore conceivable that the pancreatic carcinogenetic process and/or the maintenance of the transformed phenotype strongly rely on the dysregulated activity of the p21ras-mediated signalling. The inhibition of p21ras signalling has therefore been postulated as a possible target for anticancer therapy and might be specifically suitable for the treatment of PC.

Bisphosphonates (BPs), the most effective and widely used class of drugs in the treatment of metabolic bone disorders, including tumour-associated bone disease, are capable of inhibiting p21ras signalling (Luckman et al, 1998; GSK-3 Green, 2001). Therefore, the extensive evaluation of these compounds, and particularly the study of the recently available and more potent nitrogen-containing BPs, may suggest expanding applications of these drugs and warrant further investigation.