Anti-apoptotic gene transcription signature of salivary gland neoplasms.
BACKGROUND
Development of accurate therapeutic approaches to salivary gland neoplasms depends on better understanding of their molecular pathogenesis. Tumour growth is regulated by the balance between proliferation and apoptosis. Few studies have investigated apoptosis in salivary tumours relying almost exclusively on immunohistochemistry or TUNEL assay. Furthermore, there is no information regarding the mRNA expression profile of apoptotic genes in salivary tumors. Our objective was to investigate the quantitative expression of BCL-2 (anti-apoptotic), BAX and Caspase3 (pro-apoptotic genes) mRNAs in salivary gland neoplasms and examine the association of these data with tumour size, proliferative activity and p53 staining (parameters associated with a poor prognosis of salivary tumours patients).


METHODS
We investigated the apoptotic profile of salivary neoplasms in twenty fresh samples of benign and seven samples of malignant salivary neoplasms, using quantitative real time PCR. We further assessed p53 and ki-67 immunopositivity and obtained clinical tumour size data.


RESULTS
We demonstrated that BCL-2 mRNA is overexpressed in salivary neoplasms, leading to an overall anti-apoptotic profile. We also found an association between the anti-apoptotic index (BCL-2/BAX) with p53 immunoexpression. A higher proliferative activity was found in the malignant tumours. In addition, tumour size was associated with cell proliferation but not with the transcription of apoptotic genes.


CONCLUSIONS
In conclusion, we show an anti-apoptotic gene expression profile in salivary neoplasms in association with p53 staining, but independent of cell proliferation and tumour size.
Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. carolinacgomes@ufmg.br
Carolina Cavaliéri
CC
Gomes
Vanessa Fátima
VF
Bernardes
Marina Gonçalves
MG
Diniz
Luiz
L
De Marco
Ricardo Santiago
RS
Gomez
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3