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Prostate cancer and the androgen receptor gene

El gen del receptor del andrógeno en el cáncer de próstata

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Abstract

Carcinoma of the prostate is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the Western countries. Androgens act on the prostatic epithelial cells by binding to an intracellular protein, the androgen receptor (AR), which is a ligand-dependent transcription factor. Prostatic cells have a wide range of responses to androgens, which ultimately control both the cell division cycle and the cell differentiation. These properties of the AR makes it important for both prostatic function and cancer. The AR is codified by the AR gene, which possesses two length polymorphisms related to prostate cancer incidence. The AR gene is frequently mutated in androgen insensitive prostatic cancer that often leads to antiandrogen-driven tumor growth. There is cumulative evidence suggesting that the AR gene variability is important in various aspects of prostatic cancer, such as racial distribution, age of appearance, recurrence and response to hormones therapy. Here we discuss the most recent and relevant findings on AR gene and prostate cancer, in order provide a comprehensive interpretation of the clinical behavior of tumors at molecular levels.

Resumen

El carcinoma de próstata es el tumor maligno más frecuentemente diagnosticado y constituye la segunda causa de muerte por cáncer en los países occidentales. Los andrógenos actúan sobre el epitelio prostático mediante su unión a una proteína intracelular, el receptor de andrógenos (RA), que es un factor de transcripción génica dependiente de ligando. Las células prostáticas tienen un amplio abanico de respuestas a los andrógenos, que finalmente controlan tanto el ciclo de división celular como la diferenciación celular. Estas propiedades hacen a los andrógenos importantes para la función y la carcinogénesis prostáticas. El RA es codificado por el gen RA situado en el cromosoma X, que posee dos polimorfismos de longitud relacionados con el cáncer de próstata. El gen RA aparece frecuentemente mutado en los cánceres de próstata insensibles a los andrógenos, lo que conduce frecuentemente al crecimiento tumoral estimulado por los antiandrógenos. Se ha acumulado evidencia científica que sugiere que la variabilidad del gen RA es importante en varios aspectos del cáncer de próstata, tales como la desigual distribución racial, la edad de aparición, la frecuencia de recidivas y la respuesta a la terapia hormonal. En este artículo discutimos los hallazgos recientes más relevantes sobre el gen RA y el cáncer de próstata, tratando de proporcionar una interpretación comprensible del comportamiento de los tumores prostáticos a nivel molecular.

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Correspondence to B. Nicolás Díaz-Chico.

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Bosch, D.N., Galván, J.J.C., Ponce, N.C. et al. Prostate cancer and the androgen receptor gene. Rev Oncol 4, 228–240 (2002). https://doi.org/10.1007/BF02732507

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