Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

doi:10.1186/1471-2407-12-266

BMC Cancer. 2012; 12: 266.

Published online 2012 June 22. doi: 10.1186/1471-2407-12-266

PMCID: PMC3464886

Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

Jodie M Fleming,^1,² Erika Ginsburg,² Shannon D Oliver,¹ Paul Goldsmith,³ and Barbara K Vonderhaar²

¹Department of Biology, North Carolina Central University, 1801 Fayetteville Street, Mary Townes Science Complex, Rm 2247, Durham, NC 27707, USA

²Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, NCI, Bethesda, MD 20892-4254, USA

³Antibody Production and Purification Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

Corresponding author.

Jodie M Fleming: jodie.fleming/at/nccu.edu; Erika Ginsburg: ginsbure/at/mail.nih.gov; Shannon D Oliver: olivers/at/nccu.edu; Paul Goldsmith: paulg/at/mail.nih.gov; Barbara K Vonderhaar: vonderhb/at/mail.nih.gov

Received March 1, 2012; Accepted June 22, 2012.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca²⁺ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer.

Methods

The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H₂O₂ to detect changes in hornerin expression during induction of apoptosis/necrosis.

Results

Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization.

Conclusions

Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast cancer.

Keywords: Hornerin, S100 protein, Mammary gland, Breast cancer, Apoptosis, Protein fragmentation

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