Increased Caspase-9 Gene Expression Contrast with Normal Type V Collagen and VEGF Isoforms Gene Expression in Lung Chemical Carcinogenesis.
Edwin R Parra, Renata A Alveno, Carolina B Faustino, Paula YSS Correa, Jymenez de Morais, Walcy R Teodoro, Vera L Capelozzi. Faculdade de Medicina da Universidade de São Paulo, Brazil
Background: Recently, we demonstrated an association between decreases in type V collagen and apoptosis in human and mouse lung chemical carcinogenesis, but the mechanisms involved still remains uncertain (Parra et al 2010; Souza et al 2010). Remodeling of the tumoral microenvironment was evaluated in a model of chemical carcinogenesis in the mouse lung.
Design: Ultrastructural analysis, tridimensional reconstruction and mRNA gene expression were used to evaluate the amount, structure and genic expression of collagen V, vascular endothelial growth factor (VEFG) isoforms (120,164, 168) and caspase-9 in two groups of male Balb/c mice: a) animals that received two intraperitoneal doses of 3 g/kg urethane carcinogen (urethane group = 15); and b) animals submitted to a sham procedure, comparable to the test group (control group = 4). Both groups were sacrificed after 120 days.
Results: All the urethane animals had multiple pulmonary neoplasms. Histologically, the lung tumors present adenoid pattern and ultrastructurally they consisted predominantly of Clara cells and of cells morphologically resembling type II alveolar epithelial cells immersed in a loose stroma composed by reduced collagen fibers. Tridimensional reconstruction showed normal spatial organization of the fibers, normal synthesis in cellular cultures and normal gene expression of type V collagen and VEFG isoforms. An important significant higher Caspase-9 expression was observed in tumoral areas when compared with control group.
Conclusions: The results suggest that chemical lung carcinogenesis doesn't induce type V collagen and VEFG issoforms genes damage but increased the expression of caspase-9 gene. The decrease observed of this collagen in the tumoral parenchyma probably is caused by active destruction of the fibers after their synthesis and in this context the activation of caspase-9 probably is not sufficient to stop the growth neoplastic cells. Other studies are necessary to evaluate if these results are only causal or consequence.
Financial support: FAPESP, CNPq.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 246, Tuesday Afternoon