Activation of PyMT in β cells induces irreversible hyperplasia, but oncogene-dependent acinar cell carcinomas when activated in pancreatic progenitors Journal Article
| Authors: | Du, Y. C. N.; Klimstra, D. S.; Varmus, H. |
| Article Title: | Activation of PyMT in β cells induces irreversible hyperplasia, but oncogene-dependent acinar cell carcinomas when activated in pancreatic progenitors |
| Abstract: | It is unclear whether the cellular origin of various forms of pancreatic cancer involves transformation or transdifferentiation of different target cells or whether tumors arise from common precursors, with tumor types determined by the specific genetic alterations. Previous studies suggested that pancreatic ductal carcinomas might be induced by polyoma middle T antigen (PyMT) expressed in non-ductal cells. To ask whether PyMT transforms and transdifferentiates endocrine cells toward exocrine tumor phenotypes, we generated transgenic mice that carry tetracycline-inducible PyMT and a linked luciferase reporter. Induction of PyMT in β cells causes β-cell hyperplastic lesions that do not progress to malignant neoplasms. When PyMT is de-induced, β cell proliferation and growth cease; however, regression does not occur, suggesting that continued production of PyMT is not required to maintain the viable expanded β cell population. In contrast, induction of PyMT in early pancreatic progenitor cells under the control of Pdx1 produces acinar cell carcinomas and β-cell hyperplasia. The survival of acinar tumor cells is dependent on continued expression of PyMT. Our findings indicate that PyMT can induce exocrine tumors from pancreatic progenitor cells, but cells in the β cell lineage are not transdifferentiated toward exocrine cell types by PyMT; instead, they undergo oncogene-dependent hyperplastic growth, but do not require PyMT for survival. © 2009 Du et al. |
| Keywords: | controlled study; unclassified drug; nonhuman; pancreas cancer; pancreas; antigen expression; cell proliferation; animal cell; mouse; phenotype; animal; metabolism; animals; mice; cell survival; cell growth; luciferase; animal experiment; animal model; cell differentiation; transgenic mouse; mus musculus; mice, transgenic; stem cell; cell transformation, neoplastic; oncogenes; oncogene; cancer regression; cell transformation; reporter gene; virus antigen; genes, reporter; polyoma middle t antigen; tetracycline; transcription factor pdx 1; virus t antigen; acinar cell carcinoma; endocrine cell; pancreas function; pancreas islet beta cell; pancreas islet cell hyperplasia; antigens, polyomavirus transforming; carcinoma, acinar cell; insulin-secreting cells; luciferases |
| Journal Title: | PLoS ONE |
| Volume: | 4 |
| Issue: | 9 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2009-09-07 |
| Start Page: | e6932 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0006932 |
| PUBMED: | 19812721 |
| PROVIDER: | scopus |
| PMCID: | PMC2758666 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "Art. No.: e6932" - "Source: Scopus" |
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