Regulation of heat shock protein-70 gene transcripts in breast cancer cells during hypo and hyperthermia exposure

Abstract

BackgroundCancer cells have intrinsic property to modulate their microenvironment and resist a wide array of stimuli including temperature disparity more efficiently than healthy cells by activating several homeostatic molecular mechanisms to sustain and prevent death. Although, oncogenic hyperthermia has been proved to induce anti-tumor effects in cancer cells through various regulatory mechanisms, the other critical molecular regulators are not studied in detail. Furthermore hypothermia is the far less studied conditions in cancer cell systems. Heat shock proteins (HSPs) are primary heat response regulators. Several studies have reported key roles of HSP-90 in neoplasias. However, the role of HSP-70 transcripts in cancer cells during hypo and hyperthermic exposure remains understudied. MethodsIn present study, the role of HSP-70 gene transcripts such as HSPA1A, HSPA4, HSPA8, HSPA9 and HSPA14 in two human breast cancer cell lines such as MCF-7 and MDA-MB-231 during direct exposure to hypo and hyperthermia (ranging from 33 °C to 42 °C) has been explored in time dependent manner. ResultsBoth the cancer cell lines showed significant changes in cell survival, proliferation and apoptosis post-hypo and hyperthermic exposure. Relative gene expression analysis showed significantly elevated expression of HSP-70 transcripts more specifically HSPA8 and HSPA14 post-hyperthermia exposure. Two different proliferative natures of MCF-7 and MDA-MB-231 cell lines showed significant variation in their transcripts expression suggesting that the HSP-70 genes expression may vary critically in normal and aggressive tumor environment. ConclusionThe present study indicates significance of HSPA8 and HSPA14 in regulating sustained behavior of cancer cells in cell and time dependent manner during hypo and hyperthermic exposure.