EL HEXACLOROBENCENO COMO FACTOR DE RIESGO EN EL CANCER DE MAMA

Las alteraciones en el microambiente estrogénico podrían influir sobre el comportamiento biológico de la glándula mamaria y los tumores, llevando a lesiones preneoplásicas o a un aumento en la malignidad tumoral mamaria.

Autor:
Andrea S. Randi
Columnista Experta de SIIC

Institución:
Universidad de Buenos Aires

Artículos publicados por Andrea S. Randi

Coautores
Carolina Andrea Pontillo* Claudia Marcela Cocca** Noelia Victoria Miret* Clara Ventura*** Lorena Vanesa Zárate**** Florencia Ana Chiappini* Laura Alvarez* Diana Leonor Kleiman de Pisarev*****
Bióloga, Universidad de Buenos Aires, Buenos Aires, Argentina*
Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina**
Biotecnóloga, Universidad de Buenos Aires, Buenos Aires, Argentina***
Estudiante, Universidad de Buenos Aires, Buenos Aires, Argentina****
Química, Universidad de Buenos Aires, Buenos Aires, Argentina*****

Recepción del artículo
13 de Abril, 2017

Aprobación
9 de Enero, 2018

Primera edición
24 de Enero, 2018

Segunda edición, ampliada y corregida
22 de Agosto, 2024

doi: http://dx.doi.org/10.21840/siic/153099

EL HEXACLOROBENCENO COMO FACTOR DE RIESGO EN EL CANCER DE MAMA

Resumen
El hexaclorobenceno (HCB) es un contaminante ambiental ampliamente distribuido y un desorganizador endocrino. Su exposición crónica en humanos produce porfiria, síntomas neurológicos, trastornos inmunitarios y disfunciones tiroideas. Es un agonista débil del receptor de hidrocarburos aromáticos (AhR), un factor de transcripción que modula genes relacionados con el metabolismo de xenobióticos, la proliferación, la migración y la invasión. Nuestro objetivo es revisar los efectos del HCB en la glándula mamaria y el cáncer mamario, resumiendo los principales mecanismos de acción. El HCB aumenta el desarrollo tumoral y activa vías de señalización de c-Src/receptor del factor de crecimiento epidérmico (EGFR), mientras que disminuye la fosforilación de tirosina 537/receptor de estrógenos alfa (REalfa), promoviendo un fenotipo de mayor malignidad y metástasis pulmonar en diferentes modelos con animales. En la glándula mamaria de rata genera un microambiente estrogénico por activación del REalfa y las vías de insulina/factores de crecimiento similares a la insulina (IGF). En células de cáncer mamario humanas MCF-7 (REalfa) induce proliferación celular, promoviendo la progresión del ciclo, aumentando la ciclina D1 y la interacción p27/c-Src. En MDA-MB-231 (-REalfa) estimula la migración e invasión, así como la expresión de metaloproteasas y factor de crecimiento transformante beta 1 (TGF-beta 1). Estos estudios indican que las alteraciones en el microambiente estrogénico podrían influir el comportamiento biológico de la glándula mamaria y los tumores, lo que provoca lesiones preneoplásicas o aumento en la malignidad tumoral mamaria. Nuestros hallazgos sugieren que el HCB podría ser un factor de riesgo para la progresión del cáncer de mama humano.

Palabras clave
hexaclorobenceno, desorganizador endocrino, cáncer de mama, receptor de hidrocarburos aromáticos, c-src quinasa, metástasis, factor de crecimiento transformante-beta 1

Artículo completo
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Hexachlorobenzene as a risk factor in breast cancer

Abstract
Hexachlorobenzene (HCB) is a widespread environmental pollutant and an endocrine disruptor. Chronic exposure of humans to HCB elicits porphyria, neurologic symptoms, immune disorders and thyroid dysfunctions. It is a dioxin-like compound and a weak ligand of the AhR (aryl hydrocarbon receptor), a transcription factor that modulates genes related to detoxification, proliferation, migration and invasion. This study was carried out to revise the results of HCB action on mammary gland and breast cancer, summarizing the main ideas of its mechanism of action. HCB increases tumor development and active c-Src/EGFR (epidermal growth factor receptor) signaling pathways, while reducing tyrosine537-ER-alpha (estrogen receptor-alpha) phosphorylation, and promoting a phenotype with enhanced malignancy and lung metastasis in different animal models. In a rat mammary gland, HCB promotes an estrogenic microenvironment by activation of ER-alpha and Insulin/IGFs (insulin growth factors) pathways. HCB induces cell proliferation, promoting cell cycle progression and enhancing cyclin D1 expression and c-Src/p27 interaction in (ER-alpha) MCF-7 human breast cancer cell line. In (ER-alpha)(-) MDA-MB-231 breast cancer cells, the pesticide enhances cell migration and invasion as well as metalloproteases and TGF-beta1 (transformig growth factor-beta1) expression. In conclusion our current study suggests that alterations in the estrogenic microenvironment may influence the biological behavior of mammary gland or breast tumors, leading to preneoplastic lesions or enhanced malignancy, respectively. Our findings suggest that HCB may be a risk factor for human breast cancer progression.

Key words
hexachlorobenzene, endocrine disruptor, breast cancer, aryl hydrocarbon receptor, c-src kinase, metastasis, transforming growth factor beta 1

Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Oncología, Toxicología
Relacionadas: Bioquímica, Endocrinología y Metabolismo, Salud Ambiental, Salud Pública

Enviar correspondencia a:
Andrea S. Randi, 1121, Paraguay 2155, Buenos Aires, Argentina

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Especialidad principal:
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EL HEXACLOROBENCENO COMO FACTOR DE RIESGO EN EL CANCER DE MAMA

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