Enhanced expression of the type II transforming growth factor-β receptor is associated with decreased survival in human pancreatic cancer

Transforming growth factor-beta s (TGF-beta s) bind to the type II TGF-beta receptor (T beta RII), which then heterodimerizes with the type I TGF-beta receptor (T beta RI), thereby initiating a signaling cascade. TGF-beta s are overexpressed in pancreatic cancer, and this overexpression is associated with more aggressive disease. Although T beta RII also is overexpressed in pancreatic ductal adenocarcinoma cells in vivo, the biologic significance of this overexpression is not completely known. Therefore in this study, we characterized T beta RII expression by Northern blot analysis in 32 normal and 42 cancerous pancreatic tissues and correlated the survival of the cancer patients with T beta RII messenger RNA (mRNA) levels. Northern blot analysis revealed that, by comparison with the normal controls, T beta RII expression was increased in 19 (45%) of 42 cancer samples. Densitometric analysis of all the pancreatic tissues revealed a 3.4-fold increase (p < 0.01) in T beta RII mRNA levels in the cancer tissues by comparison with normal controls. There was a strong correlation between the expression of T beta RII and the levels of two invasion-promoting genes, plasminogen-activator-inhibitor-1 (PAI-1) and matrix-metalloproteinase-9 (MMP9). Log-rank analysis of the Kaplan-Meier survival curves indicated that patients whose tumors overexpressed T beta RII had a significantly shorter survival period than did patients whose cancers expressed low levels of T beta RII. It is suggested that T beta RII overexpression may be a marker that correlates with disease progression in pancreatic ductal adenocarcinoma.