MDM2, P53, P21WAF1 and pAKT protein levels in genesis and behaviour of adenoid cystic carcinoma.
BACKGROUND
MDM2, P53, P21(WAF1) and pAKT are proteins associated with the balance between cell death and survival. There are many hypotheses regarding the role of these proteins in salivary gland tumours. However, many molecular events that activate or inactivate regulatory genes remain unknown. The aim of this study was to evaluate and to correlate MDM2, P53, P21(WAF1) and pAKT protein expressions in adenoid cystic carcinomas (ACC).


METHODS
Twenty-two cases of ACC were evaluated by immunohistochemistry and one cell line derived from ACC was analyzed by Western Blotting and immunofluorescence techniques.


RESULTS
Strong MDM2 and pAKT, variable P53 and null P21 expressions were found in the cases analyzed, but no statistical correlation was established when comparing MDM2 and pAKT expressions in the 3 different ACC subtypes. The ACC cell line showed intense nuclear and cytoplasmatic MDM2 and pAKT expressions and null P53 and P21 expressions.


CONCLUSIONS
Results indicate that MDM2 and pAKT are related to the tumorigenesis of ACC, but they might not be directly connected to tumour progression. We also demonstrate that the pAKT pathway is active in ACC and it seems to be activating the MDM2 shuttle from the cytoplasm to the nucleus, where it phosphorylates P53 and carries it to the cytoplasm for degradation.
de Lima
Marina de Deus Moura
Mde D
Oral Pathology Department, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil.
Marques
Yonara Maria Freire Soares
YM
Alves
Sérgio de Melo
Sde M
Freitas
Vanessa Morais
VM
Soares
Fernando Augusto
FA
de Araújo
Vera Cavalcanti
VC
Pinto
Décio dos Santos
Ddos S
Mantesso
Andrea
A
D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051057:Proto-Oncogene Proteins c-akt