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Open Access Research article

A genomics approach to identify susceptibilities of breast cancer cells to “fever-range” hyperthermia

Clarissa Amaya1, Vittal Kurisetty1, Jessica Stiles1, Alice M Nyakeriga1, Arunkumar Arumugam1, Rajkumar Lakshmanaswamy1, Cristian E Botez2, Dianne C Mitchell1 and Brad A Bryan1*

Author Affiliations

1 Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 5001 El Paso Drive, MSB1 Room 2111, El Paso, Texas 79905, USA

2 Department of Physics, University of Texas, El Paso, Texas USA

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BMC Cancer 2014, 14:81  doi:10.1186/1471-2407-14-81

Published: 11 February 2014

Abstract

Background

Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility.

Methods

To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed.

Results

Bioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells.

Conclusion

These data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock.

Keywords:
Breast cancer; Hyperthermia; Heat shock; Microarray; Genomics; Gene expression