Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer.
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, Ca(2+) 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 H(2)O(2) 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.
Department of Biology, North Carolina Central University, Mary Townes Science Complex, Durham, NC 27707, USA. jodie.fleming@nccu.edu
Jodie M
JM
Fleming
Erika
E
Ginsburg
Shannon D
SD
Oliver
Paul
P
Goldsmith
Barbara K
BK
Vonderhaar
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism; D051379:Mice; D009367:Neoplasm Staging; D021381:Protein Transport; D059748:Proteolysis; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism
D002135:Calcium-Binding Proteins; C503908:HRNR protein, human; D007381:Intermediate Filament Proteins; D009418:S100 Proteins