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Apoptosis and tumor inhibition induced by human chorionic gonadotropin beta in mouse breast carcinoma

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Abstract

For many breast cancer patients, human chorionic gonadotropin beta (hCGβ), which is a subunit of a hormone produced by the trophoblast and is essential for maintaining pregnancy, is expressed in the breast cancer cells. However, the mechanism as to how the CGβ in cell affects the cancer development is not very clear. Mouse breast carcinoma 4T1 with stably hCGβ expression (4T1-hCGβ) was established and transplanted into the Balb/c mouse abdominal mammary gland. hCGβ suppressed breast cancer cell viability in vitro, and dramatically inhibited tumor growth and attenuated tumor vessel formation in vivo. An 86–88% reduction in tumor volume in animals injected with breast cancer expressing hCGβ, as opposed to those injected with breast cancer without hCGβ expression, was observed. The production of p21 was promoted by hCGβ, whereas the Cdk2 was decreasing. These indicate that p21 signal pathway is involved in this process. Significant apoptosis was also detected in hCGβ-expressing breast cancer cells as well as the enhancement of Bax protein expression. Moreover, hCGβ blocked the blood vessels formation by inhibiting the expression of MMP9 and VEGF. Further hormone secretion analyses show that the anti-tumor activity induced by hCGβ is not related to the endocrine function.

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Abbreviations

hCGβ:

human chorionic gonadotropin beta

GFP:

green fluorescent protein

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Acknowledgement

This work was supported by the grants from “863” Project of China Ministry of Science and Technology (2004AA215182) and Key Innovation Research Programs of the Chinese Academy of Sciences (KSCX2-SW-201).

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Correspondence to Jing-Pian Peng.

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Shi, SQ., Xu, L., Zhao, G. et al. Apoptosis and tumor inhibition induced by human chorionic gonadotropin beta in mouse breast carcinoma. J Mol Med 84, 933–941 (2006). https://doi.org/10.1007/s00109-006-0085-x

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  • DOI: https://doi.org/10.1007/s00109-006-0085-x

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