학술논문

SEL1L Affects Human Pancreatic Cancer Cell Cycle and Invasiveness through Modulation of PTEN and Genes Related to Cell-Matrix Interactions
Document Type
article
Source
Neoplasia: An International Journal for Oncology Research, Vol 7, Iss 11, Pp 1030-1038 (2005)
Subject
SEL1L
cell cycle
cancer invasion
extracellular matrix-related
genes
siRNA
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
1476-5586
1522-8002
Abstract
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.