In Cancer Cell this week, researchers in the US and Europe say pancreatitis-induced inflammation contributes to pancreatic cancer. It does so by inhibiting oncogene-induced senescence of cancer cells. Pancreatic acinar cells are resistant to transformation by oncogenes, but if they are exposed to limited bouts of non-acute pancreatitis and they harbor K-Ras oncogenes, they can yield pancreatic intraepithelial neoplasias and ductal adenocarcinomas, the authors write. "Pancreatitis contributes to tumor progression by abrogating the senescence barrier characteristic of low-grade pancreatic intraepithelial neoplasias," they add. "Patients with chronic pancreatitis display senescent pancreatic intraepithelial neoplasias, providing they have received anti-inflammatory drugs. These results support the concept that anti-inflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing ductal adenocarcinomas."
Also in Cancer Cell this week, researchers at the Memorial Sloan-Kettering Cancer Center present findings from a study of the connection between Mad2 gene expression and chromosomal instability. It was recently shown that inhibition of the Rb tumor suppressor pathway causes overexpression of Mad2, but whether this would lead to chromosomal instability remained unknown. In this study, the authors show that chromosomal instability in cultured cells lacking Rb proteins requires upregulation of Mad2, and that this upregulation is also necessary for chromosomal instability and tumor progression in vivo. "Mad2 is also repressed by p53 and its upregulation is required for chromosomal instability in a p53 mutant tumor model," they researchers add. "These results demonstrate that Mad2 overexpression is a critical mediator of the chromosomal instability observed upon inactivation of two major tumor suppressor pathways."
And finally in Cancer Cell this week, researchers at the University of California, Los Angeles, examine the cell autonomous role of PTEN in regulating the growth of castration-resistant prostate cancer. Alteration of the PTEN/PI3K pathway is associated with late-state and castration-resistant prostate cancer, but how PTEN loss is involved in still unclear, the authors write. In this study, the researchers show that castration-resistant growth is an property of Pten-null prostate cancer cells. "PTEN loss suppresses androgen-responsive gene expressions by modulating androgen receptor transcription factor activity," the team writes. "Our findings identify PI3K and androgen receptor pathway crosstalk as a mechanism of castration-resistant prostate cancer development, with potentially important implications for Pten-null prostate cancer etiology and therapy."