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Calcium sensing receptor down-regulates malignant cell behavior and promotes chemosensitivity in human breast cancer

Guangming Liu1, Xin Hu, Subhas Chakrabarty

  • 1Southern Illinois University School of Medicine and Simmons Cooper Cancer Institute, Springfield, IL 62702, USA.

Cell Calcium
|November 29, 2008
PubMed

Insights

Extracellular calcium (Ca2+) and the calcium-sensing receptor (CaSR) regulate breast cell growth and invasion. Loss of CaSR expression may promote cancer malignancy and drug resistance.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • The role of calcium ions (Ca2+) and the calcium-sensing receptor (CaSR) in breast tissue and breast cancer development (mammary carcinogenesis) is not well understood.
  • Investigating this ligand-receptor system is crucial for understanding breast cancer biology.

Purpose of the Study:

  • To determine the function of the Ca2+/CaSR system in regulating the biological properties of human breast cancer cells (MCF-7 and MDA-MB-435).
  • To explore the relationship between CaSR expression, survivin levels, and response to chemotherapy.

Main Methods:

  • Culturing MCF-7 and MDA-MB-435 human breast cancer cells in varying extracellular Ca2+ concentrations.
  • Measuring cellular proliferation, invasion, soft agarose growth, survivin expression (protein, gene transcription, mRNA), and response to paclitaxel.
  • Utilizing CaSR gene knockdown to assess the necessity of CaSR in cellular responses.

Main Results:

  • Physiological extracellular Ca2+ levels reduced proliferation, invasion, and soft agarose growth in both cell lines.
  • Extracellular Ca2+ also decreased survivin expression and enhanced paclitaxel-induced cytotoxicity.
  • These effects were dependent on CaSR expression; CaSR knockdown abolished the cellular responses to extracellular Ca2+.
  • Subpopulations lacking CaSR exhibited higher survivin levels and relative resistance to paclitaxel.

Conclusions:

  • Extracellular Ca2+ and CaSR form a significant system for regulating breast epithelial cell phenotype.
  • Loss of CaSR expression in breast cells may contribute to cancer development and resistance to chemotherapy drugs like paclitaxel.

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