Acinar-to-ductal metaplasia accompanies c-myc-induced exocrine pancreatic cancer progression in transgenic rodents.

06:00 EDT 26th October 2011 | BioPortfolio

Summary of "Acinar-to-ductal metaplasia accompanies c-myc-induced exocrine pancreatic cancer progression in transgenic rodents."

Several important characteristics of exocrine pancreatic tumor pathogenesis remain incompletely defined, including identification of the cell of origin. Most human pancreatic neoplasms are ductal adenocarcinomas. However, acinar cells have been proposed as the source of some ductal neoplasms through a process of acinar-to-ductal metaplasia. The oncogenic transcription factor c-myc is associated with human pancreatic neoplasms. Transgenic mice overexpressing c-myc under control of acinar cell-specific elastase (Ela) gene regulatory elements develop acinar cell carcinomas, but also mixed neoplasms that display both acinar-like neoplastic cells and duct-like neoplastic cells. In this report, we demonstrate that, first, c-myc is sufficient to induce acinar hyperplasia, though neoplastic lesions develop focally. Second, cell proliferation remains elevated in the neoplastic duct cell compartment of mixed neoplasms. Third, the proliferation/apoptosis ratio in cells from all lesion types remains constant, suggesting that differential regulation of these processes is not a feature of cancer progression in this model. Fourth, prior to development of mixed neoplasms, there is transcriptional activation of the duct cell-specific cytokeratin 19 gene promoter in multicellular foci of amylase-positive acinar neoplasms. This observation provides direct evidence for metaplasia as the mechanism underlying development of ductal neoplastic cells within the context of an acinar neoplasm, and suggests that the stimulus for this transformation acts over a multicellular domain or field within a neoplasm. Finally, focal ductal elements develop in some acinar cell carcinomas in Ela-c-myc transgenic rats, indicating that myc-associated acinar-to-ductal metaplasia is not restricted to the mouse.


Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706.

Journal Details

This article was published in the following journal.

Name: International journal of cancer. Journal international du cancer
ISSN: 1097-0215


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