Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer.
Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer.
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DOI：
10.1186/1471-2407-12-266
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发表时间：
2012-06-22
期刊：
影响因子：
3.8
通讯作者：
Vonderhaar BK
中科院分区：
文献类型：
--
作者：
Fleming JM;Ginsburg E;Oliver SD;Goldsmith P;Vonderhaar BK
最近的证据表明 S100 蛋白在乳腺癌和肿瘤进展中发挥着新的作用。这些普遍存在的蛋白质参与许多正常和病理细胞功能，包括炎症和免疫反应、Ca2+稳态、细胞骨架成分的动态以及细胞增殖、分化和死亡。我们之前的蛋白质组学分析表明，乳腺组织和细胞外基质中存在 S100 家族成员 hornerin。据报道，角蛋白存在于健康皮肤以及伤口愈合后的银屑病和再生皮肤中，表明其在炎症/免疫反应或增殖中发挥作用。在本研究中，我们研究了霍纳林在正常乳腺细胞和乳腺癌中的潜在作用。通过免疫组织化学、蛋白质印迹分析和 PCR 测量了人乳腺组织、乳腺肿瘤活检、原代乳腺细胞和乳腺癌细胞系以及小鼠乳腺组织中霍纳蛋白的表达水平和定位。针对蛋白质的 N 端和 C 端开发了抗体，用于通过荧光免疫细胞化学检测蛋白水解片段及其特定的亚细胞定位。最后，用 H2O2 处理细胞以检测细胞凋亡/坏死诱导过程中霍纳蛋白表达的变化。乳腺上皮细胞、基质成纤维细胞和巨噬细胞表达霍纳蛋白，并在乳腺发育的不同阶段表现出独特的表达调节。此外，与浸润性小叶癌和侵袭性较低的乳腺癌表型相比，浸润性导管癌中hornerin的表达降低，并且hornerin的细胞表达在诱导细胞凋亡期间发生改变。最后，我们证明了显示差异亚细胞定位的翻译后片段的存在。我们的数据为霍纳蛋白及其蛋白水解片段控制乳腺细胞功能和乳腺癌开辟了新的可能性。
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. 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. 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. Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast cancer.
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DOI：
10.1016/j.bbrc.2008.11.050
发表时间：
2009-01-16
影响因子：
3.1
作者：
Looze, Christopher;Yui, David;Leung, Lester;Ingham, Matthew;Kaler, Maryann;Yao, Xianglan;Wu, Wells W.;Shen, Rong-Fong;Daniels, Mathew P.;Levine, Stewart J.
通讯作者：
Levine, Stewart J.
影响因子：
3.4
作者：
Dumont, D;Noben, JP;Robben, J
通讯作者：
Robben, J
DOI：
10.1016/s0167-4889(98)00143-8
发表时间：
1998-12-10
影响因子：
5.1
作者：
Barraclough, R
通讯作者：
Barraclough, R
影响因子：
4.8
作者：
Makino, T;Takaishi, M;Huh, NH
通讯作者：
Huh, NH
影响因子：
2.7
作者：
Hislop, Nikki R.;Caddy, Jacinta;Jane, Stephen M.
通讯作者：
Jane, Stephen M.