Genes induced by growth arrest in a pancreatic beta cell line: identification by analysis of cDNA arrays.
Pancreatic beta cell lines are a potentially attractive source of material for cell therapy of insulin-dependent diabetes mellitus. However, induction of proliferation in post-mitotic, differentiated beta cells is likely to affect the expression of multiple genes associated with cell function, resulting in dedifferentiation. We have developed a murine beta cell line by conditional transformation with the SV40 T antigen oncoprotein. These cells can undergo reversible induction of proliferation and growth arrest. Here we utilized this model to identify differences in gene expression between proliferating and quiescent beta cells, by analyzing known beta cell genes and differentially secreted proteins, as well as by a systematic survey of a mouse cDNA array. Our findings demonstrate that growth arrest stimulates expression of the insulin gene and genes encoding components of the insulin secretory vesicles. Screening of the cDNA array revealed the activation of multiple genes following growth arrest, many of them novel genes which may be related to beta cell function. Characterization of these genes is likely to contribute to our understanding of beta cell function and the ability to employ beta cell lines in cell therapy of diabetes.
Zimmer
Y
Y
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Milo-Landesman
D
D
Svetlanov
A
A
Efrat
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002455:Cell Division / Q000235:genetics*; D002461:Cell Line, Transformed; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis*; D015536:Down-Regulation; D007328:Insulin / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011228:Prealbumin / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D053379:Chromogranin A; D002864:Chromogranins; D018076:DNA, Complementary; D007328:Insulin; D011228:Prealbumin; D012333:RNA, Messenger; D013752:Tetracycline