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| Author(s): |
Felipe Torquato Salles
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Odontologia (FO/SDO) |
| Defense date: | 2005-09-16 |
| Examining board members: |
Décio dos Santos Pinto Júnior;
Rogério Moraes de Castilho;
Ruy Gastaldoni Jaeger;
Ricardo Alves de Mesquita;
Luiz Eduardo Blumer Rosa
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| Advisor: | Décio dos Santos Pinto Júnior |
| Abstract | |
Squamous cell carcinoma raises a great interest regarding carcinogenesis and its proliferative pathways, due to the high incidence and poor prognosis. The broad genetic and proteic profiles contribute to this poor prognosis. The present study aims to better comprehend the role played by pAkt, key protein for the development of many neoplasms. Cell lines derived from oral squamous cell carcinoma (HaCat, HN6, HN19, HN30 and HN31) were induced with 10ng/ml EGF and 5ng/ml TGF β . The expressions of pAkt, cyclin D1, Bad, caspase-3 and PTEN were analyzed through immunofluorescence, western-blot and immunoprecipitation. Results showed higher pAkt and cyclin D1 expression after EGF treatment, as well as a decrease in Bad and PTEN levels, except for HN31. Immunoprecipitation revealed that pAkt prevents apoptosis through Bad direct inactivation. However, TGF β treatment revealed different results, from what expected for this tumor supressor. pAkt expression revealed to be increased in all cells lines, but stable for HN19 and HN31. HaCat exhibited decreased levels of caspase-3 and Bad, which were unaltered in HN6, augmented in HN30. HN31 revealed only Bad increased levels, and no alterations in HN19. These findings suggest the crucial role played by EGF stimulation in the studied cell lines, and a good candidate to be targeted by chemotherapeutical approaches. TGF β treatment showed discrepancies, revealing diverse behaviors in the different cell lines. An exhisting relation between TGF β receptors and pAkt pathway may not be discharged, requiring further studies. The low occurrence of apoptosis reinforces this possibility, showing how important is Akt and related pathways for neoplastic progression, and its possible relation to cellular events not described to date. (AU) | |