Expression of Inducible Hsp70 Enhances the Proliferation of MCF-7 Breast Cancer Cells and Protects Against the Cytotoxic Effects of Hyperthermia

Overview

Journal Cell Stress Chaperones

Publisher Elsevier

Specialty Cell Biology

Date 2002 Jan 25

PMID 11795468

Citations 30

Authors

J A Barnes

D J Dix

B W Collins

C Luft

J W Allen

Affiliations

Soon will be listed here.

Abstract

Heat shock proteins (Hsps) are ubiquitous proteins that are induced following exposure to sublethal heat shock, are highly conserved during evolution, and protect cells from damage through their function as molecular chaperones. Some cancers demonstrate elevated levels of Hsp70, and their expression has been associated with cell proliferation, disease prognosis, and resistance to chemotherapy. In this study, we developed a tetracycline-regulated gene expression system to determine the specific effects of inducible Hsp70 on cell growth and protection against hyperthermia in MCF-7 breast cancer cells. MCF-7 cells expressing high levels of Hsp70 demonstrated a significantly faster doubling time (39 hours) compared with nonoverexpressing control cells (54 hours). The effect of elevated Hsp70 on cell proliferation was characterized further by 5-bromo-2'deoxyuridine labeling, which demonstrated a higher number of second and third division metaphases in cells at 42 and 69 hours, respectively. Estimates based on cell cycle analysis and mean doubling time indicated that Hsp70 may be exerting its growth-stimulating effect on MCF-7 cells primarily by shortening of the G0/G1 and S phases of the cell cycle. In addition to the effects on cell growth, we found that elevated levels of Hsp70 were sufficient to confer a significant level of protection against heat in MCF-7 cells. The results of this study support existing evidence linking Hsp70 expression with cell growth and cytoprotection in human cancer cells.

Citing Articles

State of thermal tolerance in an endangered himalayan fish Tor putitora revealed by expression modulation in environmental stress related genes.

Kaur A, Ali S, Brraich O, Siva C, Pandey P Sci Rep. 2025; 15(1):5025.

PMID: 39934267 PMC: 11814232. DOI: 10.1038/s41598-025-89772-w.

Combination of magnetic hyperthermia and gene therapy for breast cancer.

Solak K, Yildiz Arslan S, Acar M, Turhan F, Unver Y, Mavi A Apoptosis. 2024; 30(1-2):99-116.

PMID: 39427089 DOI: 10.1007/s10495-024-02026-4.

Thermal necrosis in orthopedic bone tumors: experimental research.

Wang X, Brown J, Lorimer S, Jones K, Groundland J Ann Med Surg (Lond). 2023; 85(9):4372-4377.

PMID: 37663713 PMC: 10473360. DOI: 10.1097/MS9.0000000000001052.

HSP70i to subdue autoimmunity and support anti-tumor responses.

Jaishankar D, Cosgrove C, Ramesh P, Mahon J, Shivde R, Dellacecca E Cell Stress Chaperones. 2021; 26(5):845-857.

PMID: 34542825 PMC: 8492854. DOI: 10.1007/s12192-021-01229-x.

Metabolomic Identification of Anticancer Metabolites of Australian Propolis and Proteomic Elucidation of Its Synergistic Mechanisms with Doxorubicin in the MCF7 Cells.

Alsherbiny M, Bhuyan D, Radwan I, Chang D, Li C Int J Mol Sci. 2021; 22(15).

PMID: 34360606 PMC: 8346082. DOI: 10.3390/ijms22157840.

References

Lavoie J, Tanguay R, Landry J . Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J Biol Chem. 1993; 268(5):3420-9. View

Yarranton G . Inducible vectors for expression in mammalian cells. Curr Opin Biotechnol. 1992; 3(5):506-11. DOI: 10.1016/0958-1669(92)90078-w. View

Georgopoulos C, Welch W . Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol. 1993; 9:601-34. DOI: 10.1146/annurev.cb.09.110193.003125. View

Sanchez C, Padilla R, Paciucci R, Zabala J, Avila J . Binding of heat-shock protein 70 (hsp70) to tubulin. Arch Biochem Biophys. 1994; 310(2):428-32. DOI: 10.1006/abbi.1994.1188. View

Brown C, Doxsey S, White E, Welch W . Both viral (adenovirus E1B) and cellular (hsp 70, p53) components interact with centrosomes. J Cell Physiol. 1994; 160(1):47-60. DOI: 10.1002/jcp.1041600107. View

Craig E, Weissman J, Horwich A . Heat shock proteins and molecular chaperones: mediators of protein conformation and turnover in the cell. Cell. 1994; 78(3):365-72. DOI: 10.1016/0092-8674(94)90416-2. View

Suzuki K, Watanabe M . Modulation of cell growth and mutation induction by introduction of the expression vector of human hsp70 gene. Exp Cell Res. 1994; 215(1):75-81. DOI: 10.1006/excr.1994.1317. View

Wei Y, Zhao X, Kariya Y, Teshigawara K, Uchida A . Inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein (HSP) 70 expression in tumor cells. Cancer Immunol Immunother. 1995; 40(2):73-8. PMC: 11037574. DOI: 10.1007/BF01520287. View

Tsutsumi-Ishii Y, Tadokoro K, Hanaoka F, Tsuchida N . Response of heat shock element within the human HSP70 promoter to mutated p53 genes. Cell Growth Differ. 1995; 6(1):1-8. View

10.

Inoue A, Torigoe T, Sogahata K, Kamiguchi K, Takahashi S, Sawada Y . 70-kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb. Identification of a novel region of pRb-mediating protein interaction. J Biol Chem. 1995; 270(38):22571-6. DOI: 10.1074/jbc.270.38.22571. View

11.

Heads R, Yellon D, Latchman D . Differential cytoprotection against heat stress or hypoxia following expression of specific stress protein genes in myogenic cells. J Mol Cell Cardiol. 1995; 27(8):1669-78. DOI: 10.1016/s0022-2828(95)90722-x. View

12.

Li G, Mivechi N, WEITZEL G . Heat shock proteins, thermotolerance, and their relevance to clinical hyperthermia. Int J Hyperthermia. 1995; 11(4):459-88. DOI: 10.3109/02656739509022483. View

13.

Yano M, Naito Z, Tanaka S, Asano G . Expression and roles of heat shock proteins in human breast cancer. Jpn J Cancer Res. 1996; 87(9):908-15. PMC: 5921196. DOI: 10.1111/j.1349-7006.1996.tb02119.x. View

14.

Selkirk J, He C, Patterson R, Merrick B . Tumor suppressor p53 gene forms multiple isoforms: evidence for single locus origin and cytoplasmic complex formation with heat shock proteins. Electrophoresis. 1996; 17(11):1764-71. DOI: 10.1002/elps.1150171114. View

15.

Taira T, Narita T, Ariga H . A novel G1-specific enhancer identified in the human heat shock protein 70 gene. Nucleic Acids Res. 1997; 25(10):1975-83. PMC: 146679. DOI: 10.1093/nar/25.10.1975. View

16.

Mosser D, Caron A, Bourget L, Massie B . Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol. 1997; 17(9):5317-27. PMC: 232382. DOI: 10.1128/MCB.17.9.5317. View

17.

Vargas-Roig L, Fanelli M, Lopez L, Gago F, Tello O, Aznar J . Heat shock proteins and cell proliferation in human breast cancer biopsy samples. Cancer Detect Prev. 1997; 21(5):441-51. View

18.

Kaneko R, Hayashi Y, Tohnai I, Ueda M, Ohtsuka K . Hsp40, a possible indicator for thermotolerance of murine tumour in vivo. Int J Hyperthermia. 1997; 13(5):507-16. DOI: 10.3109/02656739709023549. View

19.

Oh H, Chen X, Subjeck J . Hsp110 protects heat-denatured proteins and confers cellular thermoresistance. J Biol Chem. 1998; 272(50):31636-40. DOI: 10.1074/jbc.272.50.31636. View

20.

Landel C, Potthoff S, Nardulli A, Kushner P, Greene G . Estrogen receptor accessory proteins augment receptor-DNA interaction and DNA bending. J Steroid Biochem Mol Biol. 1998; 63(1-3):59-73. DOI: 10.1016/s0960-0760(97)00073-3. View