Mutations in the BSCL2 gene cause congenital generalized lipodystrophy complicated by severe acute pancreatitis

Aims: DNA helicases play an important role in DNA replication, recombination and repair. We have previously shown a significant association of RecQ1 A159C polymorphic variant with a poor prognosis in patients with pancreatic cancer. The purpose of the current study is to explore the role of RecQ1 gene in cellular response to gemcitabine and in patient survival. Methods: RecQ1 protein expression was measured in tumor tissues of 67 patients with pancreatic cancer using immunohistochemistry and the protein expression level was analyzed in relation to overall survival. RecQ1 gene expression was knocked down by siRNA in pancreatic adenocarcinoma cell lines. Cell proliferation, apoptosis and cell cycle distribution as well as mRNA expression of DNA repair and cell cycle regulating genes were compared in cells treated with or without gemcitabine in vector control and RecQ1 knockdown cells.. Results: RecQ1 knockdown resulted in increased sensitivity (decreased proliferation and increased apoptosis) to gemcitabine treatment. RecQ1deficient cells had reduced S-Phase distribution in cells with or without gemcitabine treatment. RecQ1 knockdown down-regulated the expression of cell cycle check point signal transducers CHK1, CHK2 and RAD9, and many genes involved in S phase DNA replication and M phase regulation. Conclusions: These observations suggest that RecQ1 plays an important role in DNA repair and cell cycle regulation, which in turn affect the cellular sensitivity to gemcitabine.