RESUMEN
BACKGROUND: Prostate cancer is the second leading cause of death among men in Western countries. Genetic alterations of the estrogen receptor gene are known to be indicative of a higher risk of this disease. The estrogen receptor gene is found as two subtypes, alpha and beta. In this study the estrogen receptor alpha and beta genes were tested in 2 human prostate cancer cell lines: the hormone-sensitive PC-EW and the hormone-independent PC-OR. MATERIALS AND METHODS: Genomic DNA was isolated from 2 cell lines from metastatic prostate adenocarcinoma in hetero-transplanted male athymic nude (nu/nu) Balb/c mice. Mutation screening was performed by sequencing of exons 1-8 and intron 1 of the human estrogen receptor gene alpha, and exons 1-9 of estrogen receptor gene beta. RESULTS: No point mutations were detected in the ER gene subtypes of either cell line. Polymorphisms were found of ER-alpha in exon 1, intron 1, exon 3, 4, 5, intron 6 and exon 8 and of ER-beta in intron 2 and exon 9. CONCLUSION: Point mutations of ER-alpha and -beta are not necessary for metastatic prostate cancer, alterations in different areas of the ER genes are more often found. These polymorphisms are a part of many genetic influences that accumulate to contribute to men's overall risk for developing prostate cancer.
Asunto(s)
Adenocarcinoma/genética , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones , Neoplasias Hormono-Dependientes/genética , Mutación Puntual , Reacción en Cadena de la PolimerasaRESUMEN
Interphase fluorescence in situ hybridization (I-FISH) was used to control the gain of genomic material in 21 human oral squamous cell carcinomas (OSCC) which had been detected by comparative genomic hybridization (CGH). DNA probes for 3q27, for 5p15.2, and for the protooncogenes c-myc (8q24) and c-abl (9q34), were used for I-FISH examination of the interphase nuclei of paraffin sections of the tumors. The corresponding alphoid DNA probes for the centromeric regions of the respective chromosomes and a probe on 5q served as controls of aneusomy. Previous examinations with int2 (11q13) and erbB2 (17q11.2-13) were included for comparison. I-FISH analysis detected a gain of 3q27 in 17, of 5p15.2 in 7, of c-myc in 14, of c-abl in 10, and formerly, of int2 in 12 and of erbB2 in 10 of the examined tumors. There was an overall confirmation of the CGH findings by the I-FISH data in 63% (36-83% depending on the studied chromosomal site), and vice versa of 76% of the I-FISH results by the CGH data. Based on these results it is recommended to use a combination of both I-FISH and CGH for the detection of genomic changes in human solid tumors as the data obtained by both techniques ideally complete each other. For this reason both techniques have now enriched the spectrum of molecular histopathology.