共查询到20条相似文献,搜索用时 171 毫秒
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Lara A. Muffley Kathy Q. Zhu Loren H. Engrav Nicole S. Gibran Anne M. Hocking 《The journal of histochemistry and cytochemistry》2011,59(3):278-288
Growing evidence indicates that the melanocortin 1 receptor (MC1R) and its ligand α–melanocyte-stimulating hormone (α-MSH) have other functions in the skin in addition to pigment production. Activation of the MC1R/α-MSH signaling pathway has been implicated in the regulation of both inflammation and extracellular matrix homeostasis. However, little is known about the role of MC1R/α-MSH signaling in the regulation of inflammatory and fibroproliferative responses to cutaneous injury. Although MC1R and α-MSH localization has been described in uninjured skin, their spatial and temporal expression during cutaneous wound repair has not been investigated. In this study, the authors report the localization of MC1R and α-MSH in murine cutaneous wounds, human acute burns, and hypertrophic scars. During murine wound repair, MC1R and α-MSH were detected in inflammatory cells and suprabasal keratinocytes at the leading edge of the migrating epithelial tongue. MC1R and α-MSH protein levels were upregulated in human burn wounds and hypertrophic scars compared to uninjured human skin, where receptor and ligand were absent. In burn wounds and hypertrophic scars, MC1R and α-MSH localized to epidermal keratinocytes and dermal fibroblasts. This spatiotemporal localization of MC1R and α-MSH in cutaneous wounds warrants future investigation into the role of MC1R/α-MSH signaling in the inflammatory and fibroproliferative responses to cutaneous injury. This article contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. 相似文献
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Laura Smith Euan W. Baxter Philip A. Chambers Caroline A. Green Andrew M. Hanby Thomas A. Hughes Claire E. Nash Rebecca A. Millican-Slater Lucy F. Stead Eldo T. Verghese Valerie Speirs 《PloS one》2015,10(10)
Background
MicroRNA (miR) expression is commonly dysregulated in many cancers, including breast. MiR–92 is one of six miRs encoded by the miR-17-92 cluster, one of the best-characterised oncogenic miR clusters. We examined expression of miR–92 in the breast epithelium and stroma during breast cancer progression. We also investigated the role of miR–92 in fibroblasts in vitro and showed that down-regulation in normal fibroblasts enhances the invasion of breast cancer epithelial cells.Methodology/Principal Findings
We used laser microdissection (LMD) to isolate epithelial cells from matched normal, DCIS and invasive tissue from 9 breast cancer patients and analysed miR–92 expression by qRT-PCR. Expression of ERβ1, a direct miR–92 target, was concurrently analysed for each case by immunohistochemistry. LMD was also used to isolate matched normal (NFs) and cancer-associated fibroblasts (CAFs) from 14 further cases. Effects of miR–92 inhibition in fibroblasts on epithelial cell invasion in vitro was examined using a Matrigel™ assay. miR–92 levels decreased in microdissected epithelial cells during breast cancer progression with highest levels in normal breast epithelium, decreasing in DCIS (p<0.01) and being lowest in invasive breast tissue (p<0.01). This was accompanied by a shift in cell localisation of ERβ1 from nuclear expression in normal breast epithelium to increased cytoplasmic expression during progression to DCIS (p = 0.0078) and invasive breast cancer (p = 0.031). ERβ1 immunoreactivity was also seen in stromal fibroblasts in tissues. Where miR–92 expression was low in microdissected NFs this increased in matched CAFs; a trend also seen in cultured primary fibroblasts. Down-regulation of miR–92 levels in NFs but not CAFs enhanced invasion of both MCF–7 and MDA-MB–231 breast cancer epithelial cells.Conclusions
miR–92 is gradually lost in breast epithelial cells during cancer progression correlating with a shift in ERβ1 immunoreactivity from nuclei to the cytoplasm. Our data support a functional role in fibroblasts where modification of miR–92 expression can influence the invasive capacity of breast cancer epithelial cells. However in silico analysis suggests that ERβ1 may not be the most important miR–92 target in breast cancer. 相似文献8.
Wen-Hung Kuo Yao-Yin Chang Liang-Chuan Lai Mong-Hsun Tsai Chuhsing Kate Hsiao King-Jen Chang Eric Y. Chuang 《PloS one》2012,7(9)
Background
Triple-negative breast cancer is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible.Methodology/Principal Findings
Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated by oligonucleotide microarrays. Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A 45-gene prognostic signature giving 98% predictive accuracy in distant recurrence of our triple-negative patients was determined using the receiver operating characteristic analysis and leave-one-out cross validation. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% confidence interval (CI) 1.04–5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The 45-gene signature identified in this study revealed that TGF-β signaling of immune/inflammatory regulation may play an important role in distant metastatic invasion of triple-negative breast cancer.Conclusions/Significance
Gene expression data and recurrence information of triple-negative breast cancer were collected and analyzed in this study. A novel set of 45-gene signature was found to be statistically predictive in disease recurrence of triple-negative breast cancer. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of distant recurrence for early-stage triple-negative patients. 相似文献9.
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Jana Karbanová Ewa Missol-Kolka Ana-Violeta Fonseca Christoph Lorra Peggy Janich Hana Hollerová József Jászai Ji?í Ehrmann Zdeněk Kolá? Cornelia Liebers Stefanie Arl Danu?e ?ubrtová Daniel Freund Jaroslav Mokry Wieland B. Huttner Denis Corbeil 《The journal of histochemistry and cytochemistry》2008,56(11):977-993
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Ramesh Narayanan Sunjoo Ahn Misty D. Cheney Muralimohan Yepuru Duane D. Miller Mitchell S. Steiner James T. Dalton 《PloS one》2014,9(7)