Genetic profile of 22 pancreatic carcinoma cell lines

Abstract

The K-ras, p53, p16 and DPC4 genes are among those most frequently altered in pancreatic ductal carcinoma. We analyzed 22 cell lines for alterations in these genes by direct sequence analysis and methylation-specific polymerase chain reaction. These cell lines showed mutations in K-ras and p53 at frequencies of 91% and 95%, respectively. Alterations in p16INK4a were found in all cases and included nine homozygous deletions, seven mutations and promoter methylation in six cases. Eight cell lines (36%) had an alteration of DPC4, including one mutation and seven homozygous deletions. The most typical mutational profile involved K-ras, p53, and p16INK4a, concurrently aberrated in 20 cases (91%). Eight cell lines had alterations in all four genes. Inactivation of DPC4 was always accompanied by alteration of all of the other three genes. This comprehensive data regarding the cumulative genetic alterations in pancreatic carcinoma cell lines will be of great value for studies involving drug sensitivity or resistance that may be associated with inactivation of a particular gene or molecular pathway.

RETRACTED ARTICLE: Oncolysis of pancreatic tumour cells by a γ34.5-deleted HSV-1 does not rely upon Ras-activation, but on the PI 3-kinase pathway

“…GTP-bound Ras is able to bind and activate effector enzymes, therefore controlling cellular proliferation, survival and other aspects of cell behaviour that can contribute to the transformed phenotype. 9 It has been shown that reoviruses can take advantage of alterations in the Ras/PKR pathway, leading to lytic infection only in malignant cells but not in normal cells which they infect abortively. 10 Viruses that cannot reverse PKR activation by themselves would theoretically become, in this way, dependent on an active cellular Ras pathway for replication.…”

The Tumor Suppressor KLF11 Mediates a Novel Mechanism in Transforming Growth Factor β–Induced Growth Inhibition That Is Inactivated in Pancreatic Cancer

“…In the context of TGFh signaling in pancreatic cancer cells, the oncogenic Ras-Mek-ERK signaling cascade deserves particular attention because (a) activating K-Ras mutations are frequently found in pancreatic cancer and are also present in the pancreatic cancer cells used in this study (29)(30)(31), and (b) oncogenic K-Ras mutations frequently lead to constitutive activation of the downstream ERK-MAPK, which has been shown to be an effective antagonist of TGFh signaling (32). We therefore decided to study whether and how the Ras-Mek-ERK signaling pathway might interfere with TGFhinduced c-myc repression in pancreatic cancer cells.…”

Inhibition of Src tyrosine kinase reverts chemoresistance toward 5-fluorouracil in human pancreatic carcinoma cells: an involvement of epidermal growth factor receptor signaling

“…Multiple mutations and changes in the expression of proto-oncogenes occur at a very high frequency in pancreatic cancer (Crnogorac-Jurcevic et al, 2001;Moore et al, 2001). Various oncogenes in signaling pathways have been indicated to contribute to drug resistance, including ras, protein kinase C, src, and so on (Masumoto and Nakano, 1997).…”