Expression of dynamin immunoreactivity in experimental pancreatic tumors induced in rat by mancozeb-nitrosomethylurea.

Abstract

Dynamins are GTPases which support receptor-mediated endocytosis and bind to several tyrosine kinase receptor-associated proteins known to mediate cell proliferation and differentiation. We have recently established that dynamin expression correlates with normal neuronal (Torre et al., J. Biol. Chem., 269 (1994) 32411-32417) and acinar pancreatic cell differentiation (Cook et al., Mol. Biol. Cell, 6 (1995) 405a). To begin to understand the role of dynamin in neoplastic pancreatic cell differentiation, we have followed the expression of this protein by immunohistochemistry during the development of pancreatic tumors in a mancozeb-nitrosomethylurea (NMU)-based carcinogenesis model recently developed in our laboratory (Monis and Valentich, Carcinogenesis, 14 (1993) 929-933). After a single intraperitoneal injection (50 mg/g body wt) of this carcinogen, rats fed with mancozeb develop pancreatic focal acinar hyperplasia (FACH), dysplastic foci (DYF) displaying acinar-like and ductular-like structures, and ductular-like carcinoma in situ (CIS). After histochemical staining using a monoclonal anti-dynamin antibody, high levels of this protein are consistently observed in well-differentiated acinar tumors (FACH). In contrast, dynamin immunoreactivity is almost undetectable in more advanced lesions showing a ductular-like phenotype (ductular-like DYF and CIS). This change in the expression pattern of dynamin during the progression of acinar into ductular-like DYF and CIS lesions correlates with recent findings from our laboratory showing a differential expression pattern for dynamin in pancreatic cells during embryonic development, with ductular-like precursor cells expressing low levels of this protein. Based upon these results, we conclude that more advanced ductular-like neoplastic cells induced by the carcinogen NMU in rat pancreas behave phenotypically like pancreatic precursor cells in their pattern of expression for dynamin.

• Authors: M A Valentich, T Cook, R Urrutia
• Journal: Cancer letters (Cancer Lett) Vol. 102 Issue 1-2 Pg. 23-9 (Apr 19 1996) ISSN: 0304-3835 [Print] Ireland
• PMID: 8603375 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carcinogens
• Fungicides, Industrial
• Maneb
• Methylnitrosourea
• Receptor Protein-Tyrosine Kinases
• GTP Phosphohydrolases
• Dynamins
• mancozeb
• Zineb

Topics

• Animals
• Blotting, Northern
• Carcinogens (toxicity)
• Cell Differentiation (drug effects)
• Dynamins
• Endocytosis (physiology)
• Female
• Fungicides, Industrial (toxicity)
• GTP Phosphohydrolases (analysis, biosynthesis, physiology)
• Male
• Maneb (toxicity)
• Methylnitrosourea (toxicity)
• Pancreatic Neoplasms (chemically induced, enzymology, pathology)
• Rats
• Rats, Wistar
• Receptor Protein-Tyrosine Kinases (physiology)
• Signal Transduction (physiology)
• Zineb (toxicity)