Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis.

D-type cyclins are components of the cell-cycle engine that link cell signaling pathways and passage throughout G1 phase. We previously described the effects of overexpression cyclin D1, D2 or D3 in mouse epidermis and tumor development. We now asked whether cyclin D2 and/or cyclin D3 play a relevant role in ras-dependent tumorigenesis. Here, we described the effect of cyclin D3 and cyclin D2 overexpression in mouse skin tumor development. Notably, overexpression of cyclin D3 results in reduced tumor development and malignant progression to squamous cell carcinomas (SCC). Biochemical analysis of keratinocytes shows that overexpression of cyclin D3 results in strong reduction of cyclin D2 and its associated kinase activity. Furthermore, we found that reinstatement of cyclin D2 level in the cyclin D3/cyclin D2 bigenic mice results in a complete reversion of the inhibitory action of cyclin D3. Supporting these results, ablation of cyclin D2 results in reduced tumorigenesis and malignant progression. On the other hand, overexpression of cyclin D2 results in an increased number of papillomas and malignant progression. We conclude that cyclin D3 and cyclin D2 play opposite roles in mouse skin tumor development and that the suppressive activity of cyclin D3 is associated with cyclin D2 downregulation.

Coxiella-like infection in psittacines and a toucan.

Seven psittacine birds and a toucan (Ramphastos toco) were diagnosed as infected with Coxiella-like bacteria, based on polymerase chain reaction and bacterial 16S rRNA gene sequence obtained from each bird's liver tissue. Most of the birds exhibited lethargy and weakness for several days prior to death. Gross lesions included mild to moderate emaciation and severely enlarged and mottled pale livers and spleens. Microscopically, there was multifocal necrosis of hepatocytes with infiltration of a mixed population of inflammatory cells, including lymphocytes, heterophils, plasma cells, and macrophages randomly scattered throughout in most birds. In several birds within the macrophages there were vacuoles containing basophilic small cocco-bacilli organisms measuring about 0.5-1 microm. The spleens had increased numbers of mononuclear phagocytic system cells, some of which had vacuoles that contained similar organisms, as observed in the liver. There was inflammation in the epicardium and endocardium, interstitium of the lungs, kidney, adrenal and thyroid glands, lamina propria of the intestine, and in occasional birds in the brain, bursa of Fabricius, and bone marrow associated with similar organisms in the macrophages. Transmission electron microscopy of the liver and lungs in most birds and in the thyroid glands of one bird revealed pleomorphic round to elongated bacteria measuring about 0.45 microm in diameter and more than 1.0 microm in length. Most of these organisms contained a peripheral zone of loosely arranged electron dense material that was located immediately beneath a trilaminar membrane. Occasional organisms contained nucleoids. This is the first documentation of disease presumptively associated with Coxiella-like bacteria in birds.

Changes in gene expression during pancreatic regeneration: activation of c-myc and H-ras oncogenes in the rat pancreas.

Expression of the c-myc and H-ras oncogenes, and of several genes specifically expressed in adult rat pancreas was investigated by monitoring changes in corresponding mRNA concentrations, by dot-blot hybridization, during the early phase of regeneration following subtotal pancreatectomy. The oncogenes c-myc and H-ras were overexpressed after 12-24 and 48 h, respectively, then returned to basal levels. The concentrations of mRNAs encoding amylase, chymotrypsinogen B, and trypsinogen I decreased during the regeneration time. By contrast, proinsulin I mRNA concentration was increased at 12-48 h after surgical resection, and actin mRNA concentration was increased at 12-48 h after surgical resection, and actin mRNA concentration was increased at 12 h after subtotal pancreatectomy and remained elevated thereafter. We concluded that regeneration after subtotal pancreatectomy is accompanied by repression of certain genes that are expressed in differentiated pancreatic tissue, and that derepression of other genes may be necessary for starting and/or maintaining the process of pancreatic regeneration.

Changes in pancreatic trophism and gene expression during a prolonged fasting period in rats.

To examine the effects of fasting on trophism and gene expression in pancreas, adult male rats were deprived of food from 0-6 d. Total DNA, RNA, and proteins, and specific mRNAs for rat amylase, chymotrypsinogen B, trypsinogen I, proinsulin I, and actin (assessed by employing cloned cDNAs and dot-blot hybridization) were quantitated in pancreas. Body and pancreatic wt diminished progressively to reach 65 and 75% of initial values at the 6th d of fasting. Protein/DNA and total RNA/DNA ratios decreased 2.04 and 2.31-fold, respectively, during 6 d of fasting. The concentration of amylase, chymotrypsinogen B, trypsinogen I, and actin mRNA, expressed as cpm/microgram RNA, decreased significantly throughout the study period, whereas the decrease observed in Proinsulin I mRNA concentration was not significantly different. When mRNA concentrations were refereed to the total content of DNA, however, the decrease was significant for all messengers tested. It is concluded that the prolonged absence of nutrients in the digestive tract exerts negative trophic influence on pancreas and triggers differential changes in pancreatic gene expression. These changes are gradual, asynchronic, and nonparallel.