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Pancreatic stellate cell models for transcriptional studies of desmoplasia-associated genes. Pancreatology 2010;10(4):505-16

Date

09/18/2010

Pubmed ID

20847583

Pubmed Central ID

PMC3214918

DOI

10.1016/S1424-3903(10)80035-3

Abstract

BACKGROUND: Pancreatic stellate cells are emerging as key players in pathophysiopathological processes underlying the development of pancreatic disease, including pancreatitis and cancer. The cells are scarce in the pancreas making their isolation time and resource use consuming.

METHODS: Therefore, with the ultimate goal of facilitating mechanistic studies, here we report the isolation, characterization, and immortalization of stellate cell lines from rat and mouse origin.

RESULTS: These cell lines display morphological and molecular markers as well as non-tumorigenic characteristics similar to the frequently used hepatic counterparts. In addition, we have tested their robustness as a model for transcriptional regulatory studies. We find that these cells respond well to TGFI? signaling by triggering a distinct cascade of gene expression, some genes overlap with the TGFI? response of LX2 cells. These cells express several key chromatin proteins and epigenetic regulators involved in the regulation of gene expression, including co-repressors such as Sin3A (short-term repression), HP1 (long-term repression), as well as CBP/p300 (activation). Furthermore, these cells are well suited for Gal4-based transcriptional activation and repression assays.

CONCLUSIONS: The cell model reported here may therefore help fuel investigations in the field of signaling, transcription, and perhaps other studies on similarly exciting cellular processes. and IAP.

Author List

Mathison A, Liebl A, Bharucha J, Mukhopadhyay D, Lomberk G, Shah V, Urrutia R

Authors

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Culture Techniques
Cell Line, Transformed
Cell Survival
Fibrosis
Gene Expression Regulation, Neoplastic
Hepatic Stellate Cells
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Pancreatic Neoplasms
Pancreatic Stellate Cells
Rats
Rats, Sprague-Dawley
Transcription, Genetic
Transfection