Expression of dynamin immunoreactivity in experimental pancreatic tumors induced in rat by mancozeb-nitrosomethylurea.
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.
Valentich
M A
MA
Instituto de Biologia Celular, Cardoba, Argentina.
Cook
T
T
Urrutia
R
R
D000818:Animals; D015152:Blotting, Northern; D002273:Carcinogens / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D008297:Male; D008344:Maneb / Q000633:toxicity*; D008770:Methylnitrosourea / Q000633:toxicity*; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015038:Zineb / Q000633:toxicity*
D002273:Carcinogens; D005659:Fungicides, Industrial; D008344:Maneb; D008770:Methylnitrosourea; D020794:Receptor Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases; D034281:Dynamins; C013099:mancozeb; D015038:Zineb