Abstract
BackgroundRecent 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.MethodsThe 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.ResultsBreast 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.ConclusionsOur data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast cancer.
Highlights
Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression
We show that proteolytic fragments of hornerin have distinctive intracellular localization and that induction of apoptosis/necrosis upregulates hornerin expression in breast cells
Expression and localization of hornerin in breast tissue, mammary cells, and exosomes Proteomic analysis of the extracellular matrix of normal breast tissue revealed the presence of the S100 family
Summary
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. The S100 protein family, consisting of over 20 members, constitutes the largest subgroup of calcium binding proteins These proteins share amino acid sequence similarity as well as the functional EF-hand structure motif, which plays a key role in calcium binding through a helix-loop-helix topology. S100A2 expression was found to be reduced as breast cancer progressed from carcinoma in situ to carcinoma [9] Corresponding to this observation, S100A2 has been proposed as a tumor suppressor in early stage lung carcinogenesis [10]
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