Gene expression profiling of mantle cell lymphoma cells reveals aberrant expression of genes from the PI3K-AKT, WNT and TGFbeta signalling pathways.
Microarray studies have revealed the differential expression of several genes in mantle cell lymphoma (MCL), but it is unknown which of these differences are dependent on the transformed MCL cell itself or on the tumour microenvironment. To investigate which genes and signalling pathways are aberrantly expressed in MCL cells we used oligonucleotide microarrays to perform gene expression profiling of both purified leukaemic MCL cells and their normal counterparts, the naive B cells. A total of 106 genes were differentially expressed at least threefold in MCL cells compared with naive B cells; 63 upregulated and 43 downregulated. To validate the microarray results in a larger set of samples, we selected 10 differentially expressed genes and quantified their expression by real-time polymerase chain reaction in peripheral blood of MCL patients (n=21), purified MCL cells (n=6) and naive B cells (n=4), obtaining fully concordant results. A computer-assisted approach was used to procure specific molecular signalling pathways that were aberrantly expressed in MCL cells. Several genes related to apoptosis and to the PI3K/AKT, WNT and tumour growth factor beta signalling pathways were altered in MCL cells when compared with naive B cells. These pathways may play a significant role in the pathogenesis of MCL and deserve further investigation as candidates for new therapeutic targets.
Rizzatti
Edgar Gil
EG
Department of Clinical Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Falcão
Roberto Passetto
RP
Panepucci
Rodrigo Alexandre
RA
Proto-Siqueira
Rodrigo
R
Anselmo-Lima
Wilma Terezinha
WT
Okamoto
Oswaldo Keith
OK
Zago
Marco Antonio
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D051153:Wnt Proteins
D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D019869:Phosphatidylinositol 3-Kinases