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. 1993 May;37(3):181–186. doi: 10.1007/BF01525433

Overexpression of 27-kDa heat-shock protein in MCF-7 breast cancer cells: effects on lymphocyte-mediated killing by natural killer and γδ T cells

David M Mahvi 1,✉, Stephen W Carper 1, F Kristian Storm 1, Stephanie R Teal 1, Paul M Sondel 3
PMCID: PMC11038024  PMID: 8334681

Abstract

Overexpression of the heat-shock protein hsp27 protein in primary breast cancers has been associated with early relapse in women with breast cancer. This study was designed to determine the role of the hsp27 protein in lymphocyte recognition of estrogen-receptor(ER)-positive breast cancer cells and to assess the effect of hsp27 expression on lymphocyte-mediated lysis. The hsp27 cDNA was inserted into the pHbAPr-1-neo plasmid expression vector and driven by the constitutive actin promoter. The ER-positive MCF-7 human breast cancer cell line was then transfected with this vector and the resulting clonal cell lines were confirmed to overexpress hsp27. hsp27-transfected clonal cell lines stimulated the proliferation of fresh peripheral blood lymphocytes (PBL) significantly better than control cells transfected with the expression vector alone. When clonal γδ T cell lines were utilized as effectors, hsp27-transfected cell lines were significantly better targets for lysis than a control-transfected MCF-7 cell line. In contrast, hsp27-transfected cell lines had no increase in susceptibility to lymphokine-activated-killer- or natural-killer-mediated lysis. These results suggest that overexpression of the hsp27 protein in ER-positive MCF-7 cells stimulated the proliferation of fresh PBL and the lysis of MCF-7 cells by γδ T cell clones.

Key words: Breast cancer, Heat-shock proteins, Lymphocyte-mediated cytotoxicity

References

  • 1.Adams DJ, McGuire WL. Quantitative enzyme linked immunosorbent assay for the estrogen-regulated Mr 24000 protein in human breast tumors: correlation with estrogen and progesterone receptors. Cancer Res. 1985;45:2445. [PubMed] [Google Scholar]
  • 2.Albertini M, Gibson D, Robinson S, et al. Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine activated killer cells. J Immunother. 1992;11:30. doi: 10.1097/00002371-199201000-00004. [DOI] [PubMed] [Google Scholar]
  • 3.Arrigo A-P, Welch W. Characterization and purification of the small 28000-dalton mammalian heat shock protein. J Biol Chem. 1987;262:15359. [PubMed] [Google Scholar]
  • 4.Arrigo A-P, Suhan J, Welch W. Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein. Mol Cell Biol. 1988;8:5059. doi: 10.1128/mcb.8.12.5059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Carper SW, Rocheleau TA, Storm FK. cDNA sequence of a human heat shock protein HSP27. Nucleic Acids Res. 1990;18:6457. doi: 10.1093/nar/18.21.6457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Ciocca D, Stati A, Amprino de Castro M. Colocalization of estrogen and progesterone receptors with an estrogen regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue. Breast Cancer Res Treat. 1990;16:243. doi: 10.1007/BF01806332. [DOI] [PubMed] [Google Scholar]
  • 7.De Libero G, Casorati G, Giachino C, et al. Selection by two powerful antigens may account for the presence of the major population of human peripheral γδ T cells. J Exp Med. 1991;173:1311. doi: 10.1084/jem.173.6.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Fisch P, Malkovsky M, Braackman E, et al. γ/δT cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatability complex-restricted cytolysis. J Exp Med. 1990;171:1567. doi: 10.1084/jem.171.5.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Fisher B, Constantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989;320:479. doi: 10.1056/NEJM198902233200802. [DOI] [PubMed] [Google Scholar]
  • 10.Fuqua S, Blum-Salingaros M, McGuire W. Induction of the estrogen-regulated “24K” protein by heat shock. Cancer Res. 1989;49:4126. [PubMed] [Google Scholar]
  • 11.Gambacorti-Passerini C, Rivoltini L, Supino R, et al. Differential lysis of melanoma clones by autologous interleukin-2-activated lymphocytes: relationship with spontaneous resistance to doxorubicin. Int J Cancer. 1988;42:544. doi: 10.1002/ijc.2910420412. [DOI] [PubMed] [Google Scholar]
  • 12.Gunning P, Leavitt J, Muscat G, Ng S-Y, Kedes L. A human b-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci USA. 1987;84:4831. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Hank JA, Sosman JA, Kohler PC, et al. Depressed in vitro T cell responses concomitant with augmented interleukin-2 responses by lymphocytes from cancer patients following in vivo treatment with interleukin-2. J Biol Response Mod. 1990;9:5. [PubMed] [Google Scholar]
  • 14.Huot J, Roy G, Lambert H, Chretien P, Landry J. Increased survival after treatments with anticancer agents of Chinese hamster ovary cells expressing the human Mr 27.000 heat shock protein. Cancer Res. 1991;51:5245. [PubMed] [Google Scholar]
  • 15.Landry J, Bernier D, Chretein P, Nicole L, Tanguay R, Marceau N. Synthesis and degradation of heat shock proteins during development and decay of thermotolerance. Cancer Res. 1982;42:2457. [PubMed] [Google Scholar]
  • 16.Landry J, Chretien P, Lambert H, Hickey E, Weber L. Heat shock resistance conferred by expression of the human hsp27 gene in rodent cells. J Cell Biol. 1989;109:7. doi: 10.1083/jcb.109.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Moretti-Rojas I, Fuqua S, Montgomery R, McGuire W. A cDNA for the estradiol-regulated 24 K protein: control of mRNA levels in MCF-7 cells. Breast Cancer Res Treat. 1988;11:155. doi: 10.1007/BF01805839. [DOI] [PubMed] [Google Scholar]
  • 18.Pross HF, Maroun JA. The standardization of NK cell assays for use in studies of biological response modifiers. J Immunol. 1984;68:235. doi: 10.1016/0022-1759(84)90154-6. [DOI] [PubMed] [Google Scholar]
  • 19.Rivoltini L, Gambacorti-Passerini C, Supino R, et al. Generation and partial characterization of melanoma sublines resistant to lymphokine-activated killer (LAK) cells. Relevance to the drug resistant phenotype. Int J Cancer. 1989;43:880. doi: 10.1002/ijc.2910430524. [DOI] [PubMed] [Google Scholar]
  • 20.Thor A, Benz C, Moore D, et al. Stress response protein (srp-27) determination in primary human breast carcinomas: clinical histologic and prognostic correlations. JNCI. 1991;83:170. doi: 10.1093/jnci/83.3.170. [DOI] [PubMed] [Google Scholar]
  • 21.Weber L. Relationship of heat shock proteins and induced thermal resistance. Cell Prolif. 1992;25:101. doi: 10.1111/j.1365-2184.1992.tb01484.x. [DOI] [PubMed] [Google Scholar]

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