Expression profile of malignant and non-malignant diseases of the thyroid gland reveals altered expression of a common set of genes in goiter and papillary carcinomas.
Using cDNA microarrays with 3800 cDNA fragments, we determined the expression profile of normal thyroid tissue, goiter, adenoma and papillary carcinoma (10 samples from each class). After background correction and statistical analysis, we identified a set of 160 genes as being differentially expressed in all pair-wise comparisons. Here we demonstrate that, at least on the basis of these differentially expressed genes, a positive correlation between goiter and papillary carcinomas could be observed. We identified a common set of genes whose expression is diminished in both goiter and papillary carcinomas as compared to normal thyroid tissue. Moreover, no genes with inverse correlation in samples from goiter and papillary carcinomas could be detected. Using Real-Time PCR and/or tissue microarrays, we confirmed the altered expression of some of the identified genes. Of notice, we demonstrate that the reduced mRNA levels of p27(kip1) observed in papillary carcinomas as compared to either goiter or normal thyroid tissues (P<0.001) is accompanied by an altered protein distribution within the cell. In papillary carcinomas, P27(KIP1) is preferentially cytoplasmic as opposed to goiter or normal thyroid tissue, where P27(KIP1) is preferentially located in the nucleus. The exploitation of the data presented here could contribute to the understanding of the molecular events related to thyroid diseases and gives support to the notion that common molecular events might be related to the frequent observation of areas of papillary carcinomas in the gland of patients with goiter.
Stolf
Beatriz S
BS
Ludwig Institute for Cancer Research, São Paulo, Brazil; Instituto de Química, USP, São Paulo, Brazil.
Abreu
Cintia M
CM
Mahler-Araújo
Maria B
MB
Dellamano
Márcia
M
Martins
Waleska K
WK
de Carvalho
Marcos Brasilino
MB
Curado
Maria P
MP
Díaz
Juan P
JP
Fabri
Artur
A
Brentani
Helena
H
Carvalho
Alex F
AF
Soares
Fernando A
FA
Kowalski
Luiz P
LP
Hirata
Roberto
R
Reis
Luiz F L
LF
D002291:Carcinoma, Papillary / Q000235:genetics*; D002352:Carrier Proteins / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020869:Gene Expression Profiling; D006042:Goiter / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics*; D046888:Tissue Array Analysis
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27