SEL1L affects human pancreatic cancer cell cycle and invasiveness through modulation of PTEN and genes related to cell-matrix interactions.
Previously, it was reported that SEL1L is able to decrease the aggressive behavior of human pancreatic tumor cells both in vitro and in vivo. To gain insights into the involvement of SEL1L in tumor invasion, we performed gene expression analysis on the pancreatic cancer cell line Suit-2 subjected to two complementary strategies: upregulation and downregulation of SEL1L expression by stable transfection of the entire cDNA under an inducible promoter and by RNA-mediated interference. SuperArray and real-time analysis revealed that SEL1L modulates the expression of the matrix metalloproteinase inhibitors TIMP1 (P < .04-.03) and TIMP2 (P < .03-.05), and the PTEN gene (P < .03-.05). Gene expression modulations correlate with the decrease in invasive ability (P < .05) and in accumulation of SEL1L-expressing cells in G1. Taken together, our data indicate that SEL1L alters the expression of mediators involved in the remodeling of the extracellular matrix by creating a microenvironment that is unfavorable to invasive growth and by affecting cell cycle progression through promotion of G1 accumulation.
Cattaneo
Monica
M
Institute for Biomedical Technologies, National Research Council, Segrate 20090, Milan, Italy.
Fontanella
Enrico
E
Canton
Cristina
C
Delia
Domenico
D
Biunno
Ida
I
D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D011506:Proteins / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics
D011506:Proteins; C117384:SEL1L protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human