Loss of primary cilia occurs early in breast cancer development

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• 作者：Ina Menzl (1)
  Lauren Lebeau (2)
  Ritu Pandey (1)
  Nadia B Hassounah (1)
  Frank W Li (3)
  Ray Nagle (1) (2)
  Karen Weihs (1) (4)
  Kimberly M McDermott (1) (3) (5)
  
  1. The University of Arizona Cancer Center ; University of Arizona ; Tucson ; AZ ; USA
  2. Department of Pathology ; University of Arizona Medical Center ; Tucson ; AZ ; USA
  3. Department of Cellular and Molecular Medicine ; University of Arizona ; Tucson ; AZ ; USA
  4. Department of Psychiatry ; University of Arizona Medical Center ; Tucson ; AZ ; USA
  5. Bio5 Institute ; University of Arizona ; Tucson ; AZ ; USA
  
• 关键词：Primary cilia ; Invasive breast cancer ; Carcinoma in situ ; Cancer ; associated stroma ; Ciliogenesis ; Cilia length
• 刊名：Cilia
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：3
• 期：1
• 全文大小：1,946 KB
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• 刊物主题：Cell Biology; Developmental Biology; Human Genetics; Molecular Medicine; Biochemistry, general; Receptors;
• 出版者：BioMed Central
• ISSN：2046-2530

文摘

Background Primary cilia are microtubule-based organelles that protrude from the cell surface. Primary cilia play a critical role in development and disease through regulation of signaling pathways including the Hedgehog pathway. Recent mouse models have also linked ciliary dysfunction to cancer. However, little is known about the role of primary cilia in breast cancer development. Primary cilia expression was characterized in cancer cells as well as their surrounding stromal cells from 86 breast cancer patients by counting cilia and measuring cilia length. In addition, we examined cilia expression in normal epithelial and stromal cells from reduction mammoplasties as well as histologically normal adjacent tissue for comparison. Results We observed a statistically significant decrease in the percentage of ciliated cells on both premalignant lesions as well as in invasive cancers. This loss of cilia does not correlate with increased proliferative index (Ki67-positive cells). However, we did detect rare ciliated cancer cells present in patients with invasive breast cancer and found that these express a marker of basaloid cancers that is associated with poor prognosis (Cytokeratin 5). Interestingly, the percentage of ciliated stromal cells associated with both premalignant and invasive cancers decreased when compared to stromal cells associated with normal tissue. To understand how cilia may be lost during cancer development we analyzed the expression of genes required for ciliogenesis and/or ciliary function and compared their expression in normal versus breast cancer samples. We found that expression of ciliary genes were frequently downregulated in human breast cancers. Conclusions These data suggest that primary cilia are lost early in breast cancer development on both the cancer cells and their surrounding stromal cells.