Cadmium promotes the proliferation of triple-negative breast cancer cells through EGFR-mediated cell cycle regulation.
Toxicol Appl Pharmacol
; 289(1): 98-108, 2015 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-26385184
Cadmium (Cd) is a carcinogenic metal which is implicated in breast cancer by epidemiological studies. It is reported to promote breast cancer cell growth in vitro through membrane receptors. The study described here examined Cd-mediated growth of non-metastatic human breast cancer derived cells that lack receptors for estrogen, progesterone, and HER2. Treatment of triple-negative HCC 1937 cells with 0.1-0.5 µM Cd increased cell growth by activation of AKT and ERK. Accelerated cell cycle progression was achieved by increasing the levels of cyclins A, B, and E, as well as those of CDKs 1 and 2. Although triple negative cells lack estrogen receptor, they express high levels of EGFR. Therefore, further studies on HCC 1937 and another triple-negative cell line, HCC 38, were conducted using specific siRNA and an inhibitor of EGFR to determine whether EGFR was responsible for mediating the effect of Cd. The results revealed that in both cell types EGFR was not only activated upon Cd treatment, but was also essential for the downstream activation of AKT and ERK. Based on these observations, it is concluded that, in breast cancer cells lacking estrogen receptor, sub-micromolar concentration of Cd can promote cell proliferation. Furthermore, that EGFR plays a critical role in this process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cadmio
/
Ciclo Celular
/
Proliferación Celular
/
Neoplasias de la Mama Triple Negativas
/
Receptores ErbB
Límite:
Female
/
Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Estados Unidos