RESUMO
Non-small cell lung cancer (NSCLC)-associated epidermal growth factor receptor (EGFR) mutants are constitutively active and induce ligand-independent transformation in non-malignant cell lines. We investigated the possibility that the ability of mutant EGFRs to transform cells reflects a constitutive cooperativity with Src using a system in which the overexpression of mutant, but not wild-type, EGFR induced anchorage-independent cell growth. Src was constitutively activated and showed enhanced interaction with mutant EGFRs, suggesting that constitutive EGFR-Src cooperativity may contribute to mutant EGFR-mediated oncogenesis. Indeed, the mutant EGFR-mediated cell transformation was inhibited by Src- as well as EGFR-directed inhibitors. Importantly, a tyrosine to phenylalanine mutation of the major Src phosphorylation site on EGFR, Y845, reduced the constitutive phosphorylation of NSCLC-EGFR mutants, as well as that of STAT3, Akt, Erk and Src, and reduced the mutant EGFR-Src association as well as proliferation, migration and anchorage-independent growth. Reduced anchorage-independent growth and migration were also observed when dominant-negative-Src was expressed in mutant EGFR-expressing cells. Overall, our findings show that mutant EGFR-Src interaction and cooperativity play critical roles in constitutive engagement of the downstream signaling pathways that allow NSCLC-associated EGFR mutants to mediate oncogenesis, and support the rationale to target Src-dependent signaling pathways in mutant EGFR-mediated malignancies.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Quinases da Família src/fisiologia , Animais , Movimento Celular , Proliferação de Células , Humanos , Camundongos , Células NIH 3T3 , Fosforilação , Transdução de SinaisRESUMO
The loss of a permanent molar in young adolescent patient creates a need for early space maintenance and restoration of function. To establish function and esthetics short-term treatments include interim restorative approaches. This paper describes a functional, cost-effective stainless steel crown bridge as an interim restoration after the loss of permanent first molar in an early adolescent dentition.
Assuntos
Coroas , Prótese Parcial Fixa , Prótese Parcial Temporária , Dente Molar , Aço Inoxidável , Resinas Acrílicas , Adolescente , Dente Suporte , Cárie Dentária/terapia , Planejamento de Dentadura , Estética Dentária , Feminino , Seguimentos , Humanos , Mantenedor de Espaço em Ortodontia/instrumentação , Extração Dentária , Fraturas dos Dentes/terapiaRESUMO
Reattachment of the original tooth fragment to the fractured tooth provides benefits of maintaining the tooth's shape, colour texture and translucency in the restoration. This paper describes fragment reattachment of a non-vital central incisor five months after trauma.
