Differential Expression of Steroid Receptors, Hsp27, and PS2 in a Series of Drug Resistant Human Breast Tumor Cell Lines Derived Following Exposure to Antitumor Drugs or to Fractionated X-irradiation

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 1993 Jan 1

PMID 8400321

Citations 7

Authors

R D Whelan

B T Hill

Affiliations

Soon will be listed here.

Abstract

This study examined whether levels of estrogen receptor (ER), progesterone receptor (PR), and expression of estrogen regulated pS2 and/or heat shock protein (hsp) 27 were associated with drug resistance in a series of MCF-7 sublines expressing modest (i.e. 3- to 14-fold), yet clinically relevant, levels of resistance to vincristine (VCR). These sublines were variously derived following pulsed exposures to VCR, to fractionated X-irradiation, or to alternating drug and X-ray treatments. This selection procedure more closely reflects the clinical treatment of breast tumors than the use of continuous drug exposures. The drug-selected sublines exhibited the classical multidrug resistance phenotype (MDR) characterized by cross-resistance to vinblastine (VLB), etoposide (VP-16), and Adriamycin (ADR), overexpression of P-glycoprotein (Pgp), impaired accumulation of [3H]-VCR and of Rhodamine-123 (Rh 123), and altered activities of certain drug detoxification enzymes. This classic MDR phenotype was associated with a lack of mitogenic response to estrogen or antiestrogen, related to loss of detectable ER and PR; consistent with these data, neither pS2 nor hsp27 expression was detectable. In contrast, X-ray-pretreated VCR-resistant cells (MCF/DXR-10) cells exhibited a distinctive resistance phenotype proving cross-resistant to VLB and VP-16 but not to ADR, and Pgp overexpression was not detectable. Furthermore, these VCR-resistant DXR-10 cells retained parental levels of ER and PR, exhibited sensitivity to estrogen and 4-hydroxytamoxifen, and expressed detectable levels of pS2 and hsp27. Comparable characteristics to these MCF-7/DXR-10 cells were also identified in a similarly-derived X-ray-pretreated VCR-resistant subline of the ZR-75-1 human breast tumor cell line. These data therefore indicate that functional ER are frequently, but not invariably, modified in tumor cells which express resistance to multiple drugs.

Citing Articles

Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells.

Owen S, Zhao H, Dart A, Wang Y, Ruge F, Gao Y Int J Oncol. 2016; 49(5):1839-1847.

PMID: 27600495 PMC: 5063420. DOI: 10.3892/ijo.2016.3685.

Increased expression of HSP27 linked to vincristine resistance in human gastric cancer cell line.

Yang Y, Sun X, Cheng A, Zhang G, Yi H, Sun Y J Cancer Res Clin Oncol. 2008; 135(2):181-9.

PMID: 18758817 DOI: 10.1007/s00432-008-0460-9.

A 27 kDa heat shock protein that has anomalous prognostic powers in early and advanced breast cancer.

Love S, King R Br J Cancer. 1994; 69(4):743-8.

PMID: 8142264 PMC: 1968803. DOI: 10.1038/bjc.1994.140.

Modified multiple drug resistance phenotype of Chinese hamster ovary cells selected with X-rays and vincristine versus X-rays only.

McClean S, Hill B Br J Cancer. 1994; 69(4):711-6.

PMID: 7908216 PMC: 1968820. DOI: 10.1038/bjc.1994.134.

Differential cytotoxic effects of docetaxel in a range of mammalian tumor cell lines and certain drug resistant sublines in vitro.

Hill B, Whelan R, Shellard S, McClean S, Hosking L Invest New Drugs. 1994; 12(3):169-82.

PMID: 7896535 DOI: 10.1007/BF00873957.

References

Rios M, Macias A, Perez R, Lage A, Skoog L . Receptors for epidermal growth factor and estrogen as predictors of relapse in patients with mammary carcinoma. Anticancer Res. 1988; 8(1):173-6. View

Koerner F, Goldberg D, Edgerton S, Schwartz L . pS2 protein and steroid hormone receptors in invasive breast carcinomas. Int J Cancer. 1992; 52(2):183-8. DOI: 10.1002/ijc.2910520205. View

Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P . Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982; 10(24):7895-903. PMC: 327057. DOI: 10.1093/nar/10.24.7895. View

Hill B . Interactions between antitumour agents and radiation and the expression of resistance. Cancer Treat Rev. 1991; 18(3):149-90. DOI: 10.1016/0305-7372(91)90006-l. View

Goldie J, Coldman A, Gudauskas G . Rationale for the use of alternating non-cross-resistant chemotherapy. Cancer Treat Rep. 1982; 66(3):439-49. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Fairbanks G, Steck T, Wallach D . Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry. 1971; 10(13):2606-17. DOI: 10.1021/bi00789a030. View

Bellamy A, Whelan R, Lock R, Hill B . Effects of fractionated X-irradiation on subsequent response to acute X-irradiation in two human tumour cell lines in vitro. Int J Radiat Biol Relat Stud Phys Chem Med. 1987; 51(4):681-91. DOI: 10.1080/09553008414552211. View

Riordan J, Deuchars K, Kartner N, Alon N, Trent J, Ling V . Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature. 1985; 316(6031):817-9. DOI: 10.1038/316817a0. View

10.

Church G, Gilbert W . Genomic sequencing. Proc Natl Acad Sci U S A. 1984; 81(7):1991-5. PMC: 345422. DOI: 10.1073/pnas.81.7.1991. View

11.

Rio M, Bellocq J, Gairard B, Rasmussen U, Krust A, Koehl C . Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2. Proc Natl Acad Sci U S A. 1987; 84(24):9243-7. PMC: 299729. DOI: 10.1073/pnas.84.24.9243. View

12.

Vickers P, Dickson R, Shoemaker R, Cowan K . A multidrug-resistant MCF-7 human breast cancer cell line which exhibits cross-resistance to antiestrogens and hormone-independent tumor growth in vivo. Mol Endocrinol. 1988; 2(10):886-92. DOI: 10.1210/mend-2-10-886. View

13.

Huot J, Roy G, Lambert H, Chretien P, Landry J . Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. Cancer Res. 1991; 51(19):5245-52. View

14.

Heikkila R, Cabbat F . A sensitive assay for superoxide dismutase based on the autoxidation of 6-hydroxydopamine. Anal Biochem. 1976; 75(2):356-62. DOI: 10.1016/0003-2697(76)90089-0. View

15.

Whelan R, Waring C, Wolf C, Hayes J, Hosking L, Hill B . Over-expression of P-glycoprotein and glutathione S-transferase pi in MCF-7 cells selected for vincristine resistance in vitro. Int J Cancer. 1992; 52(2):241-6. DOI: 10.1002/ijc.2910520215. View

16.

Harris J, Lippman M, Veronesi U, Willett W . Breast cancer (3). N Engl J Med. 1992; 327(7):473-80. DOI: 10.1056/NEJM199208133270706. View

17.

Paglia D, Valentine W . Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967; 70(1):158-69. View

18.

Riordan J, Ling V . Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. J Biol Chem. 1979; 254(24):12701-5. View

19.

Lock R, Hill B . Differential patterns of anti-tumour drug responses and mechanisms of resistance in a series of independently-derived VP-16-resistant human tumour cell lines. Int J Cancer. 1988; 42(3):373-81. DOI: 10.1002/ijc.2910420312. View

20.

Hill B, Whelan R, Hosking L, Shellard S, Bedford P, Lock R . Interactions between antitumor drugs and radiation in mammalian tumor cell lines: differential drug responses and mechanisms of resistance following fractionated X-irradiation or continuous drug exposure in vitro. NCI Monogr. 1988; (6):177-81. View