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

10:43 EDT 24th October 2014 | 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.

Affiliation

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
Pages:

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Medical and Biotech [MESH] Definitions

The major component (about 80%) of the PANCREAS composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as TRYPSINOGEN; LIPASE; AMYLASE; and RIBONUCLEASE. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the DUODENUM.

A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.

Star-shaped, myofibroblast-like cells located in the periacinar, perivascular, and periductal regions of the EXOCRINE PANCREAS. They play a key role in the pathobiology of FIBROSIS; PANCREATITIS; and PANCREATIC CANCER.

A malabsorption condition resulting from greater than 10% reduction in the secretion of pancreatic digestive enzymes (LIPASE; PROTEASES; and AMYLASE) by the EXOCRINE PANCREAS into the DUODENUM. This condition is often associated with CYSTIC FIBROSIS and with chronic PANCREATITIS.

A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer.

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