Overexpression of CRKL correlates with malignant cell proliferation in breast cancer

Tumour Biol. 2013 Oct;34(5):2891-7. doi: 10.1007/s13277-013-0851-7. Epub 2013 May 19.

Abstract

Crk-like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. However, the expression pattern of CRKL protein and its clinical significance in human breast cancers have not been well characterized. In this study, expression of CRKL was evaluated in 108 human invasive ductal carcinoma (IDC) tissues by immunohistochemistry. CRKL protein was upregulated in the cancer tissues compared with adjacent normal mammary glands. Overexpression of CRKL was found in 40 of 108 (37.03 %) breast cancer samples and correlated with advanced p-tumor-node-metastasis stage (p = 0.002), nodal metastasis (p = 0.0323), and tumor size (p = 0.0075). In addition, overexpression of CRKL in the MDA-MB-435 cell line promoted cell proliferation, and small interfering RNA knockdown of CRKL in the MDA-MB-453 cell line inhibited proliferation. Further analysis of cell cycle-related molecules showed that CRKL induced cyclin D1 and phosphorylated extracellular signal-regulated kinase expression. In conclusion, this study demonstrated that overexpression of CRKL correlated with progression and malignant proliferation of human breast cancers.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Humans
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational

Substances

  • Adaptor Proteins, Signal Transducing
  • CCND1 protein, human
  • CRKL protein
  • Nuclear Proteins
  • Cyclin D1
  • Extracellular Signal-Regulated MAP Kinases