Expression of genes related to apoptosis, cell cycle and signaling pathways are independent of TP53 status in urinary bladder cancer cells.
Urinary bladder cancer is the fourth most common malignancy in the Western world. Transitional cell carcinoma (TCC) is the most common subtype, accounting for about 90% of all bladder cancers. The TP53 gene plays an essential role in the regulation of the cell cycle and apoptosis and therefore contributes to cellular transformation and malignancy; however, little is known about the differential gene expression patterns in human tumors that present with the wild-type or mutated TP53 gene. Therefore, because gene profiling can provide new insights into the molecular biology of bladder cancer, the present study aimed to compare the molecular profiles of bladder cancer cell lines with different TP53 alleles, including the wild type (RT4) and two mutants (5637, with mutations in codons 280 and 72; and T24, a TP53 allele encoding an in-frame deletion of tyrosine 126). Unsupervised hierarchical clustering and gene networks were constructed based on data generated by cDNA microarrays using mRNA from the three cell lines. Differentially expressed genes related to the cell cycle, cell division, cell death, and cell proliferation were observed in the three cell lines. However, the cDNA microarray data did not cluster cell lines based on their TP53 allele. The gene profiles of the RT4 cells were more similar to those of T24 than to those of the 5637 cells. While the deregulation of both the cell cycle and the apoptotic pathways was particularly related to TCC, these alterations were not associated with the TP53 status.
Faculdade de Medicina de Botucatu, Botucatu Medical School, UNESP-São Paulo State University, Botucatu, SP, 18618-000, Brazil. nicioli@fmb.unesp.br
Glenda N
GN
da Silva
Adriane F
AF
Evangelista
Danielle A
DA
Magalhães
Cláudia
C
Macedo
Michelle C
MC
Búfalo
Elza T
ET
Sakamoto-Hojo
Geraldo A S
GA
Passos
Daisy M F
DM
Salvadori
D017209:Apoptosis / Q000235:genetics*; D001499:Bayes Theorem; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53