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Chaperoning of estrogen receptor and induction of mammary gland proliferation by neuronal protein synuclein gamma

Oncogene volume 26, pages 2115–2125 (2007)Cite this article

Abstract

Synucleins are emerging as central players in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein γ (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly associated with breast cancer progression. Using transgenic mouse model, we demonstrated a role of SNCG in induction of highly proliferative pregnancy-like phenotype of mammary epithelial cells and branching morphology. SNCG participated in the heat shock protein-based multiprotein chaperone complex for steroid receptor signaling. Expression of SNCG in mammary epithelium resulted in a significant stimulation of ERα transcriptional activity. SNCG-induced mammary gland proliferation can be effectively blocked by antiestrogen and ovariectomy, indicating that the induced proliferation is mediated by ERα signaling and requires estrogen stimulation. These data indicate the chaperone activity of SNCG on stimulation of steroid receptor signaling in mammary gland and, thus induces extensive mammary gland proliferation and contributes to the hormonal impact on mammary tumorigenesis.

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Abbreviations

AD:

Alzheimer's disease

BCSG1:

breast cancer specific gene 1

Cat-D:

Cathepsin D

ERα:

estrogen receptor α

Hsp:

heat shock protein

PD:

Parkinson's disease

PR:

progesterone receptor

SNCA:

α synuclein

SNCB:

β synuclein

SNCG:

γ synuclein

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Acknowledgements

This study was supported in part by grant (99-028-01-CCE) from American cancer Society, grants (W81XWH-04-1-0569) from the United States Army Medical Research and Development Command.

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Authors and Affiliations

  1. Department of Radiation Oncology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, The Feinstein Institute for Medical Research, New Hyde Park, NY, USA

    Y E Liu, W Pu, D Shi, R Dackour & Y E Shi

  2. Division of Molecular Oncology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

    Y Jiang

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  1. Y E Liu
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  2. W Pu
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  3. Y Jiang
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  4. D Shi
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  5. R Dackour
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Correspondence to Y E Shi.

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Liu, Y., Pu, W., Jiang, Y. et al. Chaperoning of estrogen receptor and induction of mammary gland proliferation by neuronal protein synuclein gamma. Oncogene 26, 2115–2125 (2007). https://doi.org/10.1038/sj.onc.1210000

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