Anti-apoptotic effect of claudin-1 in tamoxifen-treated human breast cancer MCF-7 cells

BMC Cancer. 2010 Oct 12:10:548. doi: 10.1186/1471-2407-10-548.

Abstract

Background: Claudin-1 is a membrane protein of tight junctions, and is associated with the development of various cancers. However, the significance of claudin-1 expression in cancer cells is not well understood. Here, we showed for the first time the anti-apoptotic effect of claudin-1 in human breast cancer MCF-7 cells.

Methods: Human breast cancer MCF-7 and T47 D cells were treated with or without tamoxifen, siRNA against claudin-1, or tamoxifen and claudin-1 siRNA. The samples were analyzed by RT-PCR, Western blotting or immunofluorescent staining.

Results: The expression of claudin-1 was upregulated in tamoxifen-treated MCF-7 cells, whereas the expression of claudin-1 was not altered in tamoxifen-treated T47 D cells. Knockdown of claudin-1 by siRNA increased the amount of poly (ADP-ribose) polymerase (PARP) regardless of tamoxifen treatment in MCF-7 cells, but not T47 D cells. In the cell membranes of the MCF-7 cells, tamoxifen treatment increased the amount of claudin-1, but decreased the amount of β-catenin. Claudin-1 siRNA increased the amount of E-cadherin in the cytoplasm of the MCF-7 cells as well as the amount of β-catenin in their cell membranes.

Conclusion: These results indicate that claudin-1 has anti-apoptotic effects, and is involved in the regulation of the expression and subcellular localization of β-catenin and E-cadherin in MCF-7, but not T47 D cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology
  • Apoptosis*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cadherins / biosynthesis
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Claudin-1
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Membrane Proteins / metabolism*
  • RNA, Small Interfering / metabolism
  • Tamoxifen / pharmacology*
  • beta Catenin / biosynthesis

Substances

  • Antineoplastic Agents, Hormonal
  • CLDN1 protein, human
  • Cadherins
  • Claudin-1
  • Membrane Proteins
  • RNA, Small Interfering
  • beta Catenin
  • Tamoxifen