Reversal of estrogen-resistance in murine mammary adenocarcinomas

From mouse mammary progestin-dependent (PD) adenocarcinomas induced with medroxyprogesterone acetate (MPA) we developed several in vivo lines that are maintained by subcutaneous syngeneic passages in MPA-treated mice and express estrogen (ER) and progesterone receptors (PR). Although most lines rema...

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Autor principal: Montecchia, M.F
Otros Autores: Molinolo, A., Lanari, C.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 1999
Acceso en línea:Registro en Scopus
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024 7 |2 scopus  |a 2-s2.0-0032981806 
024 7 |2 cas  |a Antineoplastic Agents, Hormonal; Drug Implants; Estradiol, 50-28-2; Medroxyprogesterone 17-Acetate, 71-58-9; Progestins; Receptors, Estrogen; Receptors, Progesterone 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a BCTRD 
100 1 |a Montecchia, M.F. 
245 1 0 |a Reversal of estrogen-resistance in murine mammary adenocarcinomas 
260 |c 1999 
270 1 0 |m Lanari, C.; IBYME, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina 
506 |2 openaire  |e Política editorial 
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504 |a Axelrod, D.M., Menendez-Botet, C.J., Kinne, D.W., Osborne, M.P., Levels of estrogen and progesterone receptor proteins in patients with breast cancer during various phases of menses (1988) Cancer Invest, 6, pp. 7-14 
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520 3 |a From mouse mammary progestin-dependent (PD) adenocarcinomas induced with medroxyprogesterone acetate (MPA) we developed several in vivo lines that are maintained by subcutaneous syngeneic passages in MPA-treated mice and express estrogen (ER) and progesterone receptors (PR). Although most lines remained PD, with time some progestin-independent (PI) variants arose. Both PD and PI tumors regress with estrogen treatment although estrogen-resistant variants may also arise. The object of this paper was to investigate the reversibility of estrogen-resistance and its possible relation with hormone receptor down-regulation. Tumor regression was induced in a progestin-independent tumor line (BET) by treatment with a 5 mg 17β-estradiol (E2) silastic pellet. One of the tumors started to grow disclosing an estrogen-resistant pattern of growth. This tumor line (BET-R) was transplanted into E2-treated and untreated animals (n = 4-6), selecting for the next passage tumors growing in treated animals. Seven new sublines were obtained at different passages by selecting for the next passage the tumors that had grown in untreated mice (BET-Ra-BET-Rg), until no tumors grew in E2-treated mice. ER and PR were measured by a ligand-binding, dextran-coated charcoal method using a single saturating point. From the seven sublines initiated, the first four proved to be reversible after 3-6 generation transplantation and the last three did not revert. A difference in PR expression between BET and BET-R (p < 0.05) was registered, but it did not correlate with the specific hormone behavior since two reverted lines had a pattern similar to that of BET and the other two were similar to BET-R. The expression of PR was higher in E2-treated mice (p < 0.05) and highly variable in the parental line. This led us to study the expression of PR at different stages of the estrous cycle. Higher levels of PR were observed in proestrous, estrous, and metestrous (p < 0.05) than in diestrous, and undetectable levels were found in ovariectomized mice. No differences in ER expression were detected during the estrous cycle. It can be concluded that under certain experimental conditions, estrogen-resistance is a reversible phenomenon. The experimental manipulation of hormone resistance may help develop strategies to modify the response to anti-hormones in humans.  |l eng 
536 |a Detalles de la financiación: Fundación Alberto J. Roemmers 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas, PIA: PMT.PICT 0446 
536 |a Detalles de la financiación: This work was supported by CONICET grant: PIA: PMT.PICT 0446, Fundación Sales, Fundación Roemmers, and Schering Argentina. We are also grateful to Dr. Gador Laboratories for supplying MPA. 
593 |a Lab. of Hormonal Carcinogenesis, Inst. Biologia y Med. Exp. (IBYME), CONICET, Buenos Aires, Argentina 
593 |a IBYME, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina 
690 1 0 |a ESTROGENS 
690 1 0 |a HORMONE INDEPENDENCE 
690 1 0 |a HORMONE RESISTANCE 
690 1 0 |a MAMMARY ADENOCARCINOMAS 
690 1 0 |a MICE 
690 1 0 |a REVERSIBILITY 
690 1 0 |a ESTRADIOL 
690 1 0 |a ESTROGEN 
690 1 0 |a ESTROGEN RECEPTOR 
690 1 0 |a GESTAGEN 
690 1 0 |a HORMONE RECEPTOR 
690 1 0 |a MEDROXYPROGESTERONE ACETATE 
690 1 0 |a PROGESTERONE RECEPTOR 
690 1 0 |a SILASTIC 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ARTICLE 
690 1 0 |a BREAST ADENOCARCINOMA 
690 1 0 |a DRUG RESISTANCE 
690 1 0 |a ESTROGEN THERAPY 
690 1 0 |a ESTRUS CYCLE 
690 1 0 |a HORMONE RESISTANCE 
690 1 0 |a LIGAND BINDING 
690 1 0 |a MOUSE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN EXPRESSION 
690 1 0 |a RECEPTOR DENSITY 
690 1 0 |a RECEPTOR DOWN REGULATION 
690 1 0 |a TUMOR REGRESSION 
690 1 0 |a ADENOCARCINOMA 
690 1 0 |a ANIMALS 
690 1 0 |a ANTINEOPLASTIC AGENTS, HORMONAL 
690 1 0 |a CELL DIVISION 
690 1 0 |a DRUG IMPLANTS 
690 1 0 |a DRUG RESISTANCE, NEOPLASM 
690 1 0 |a ESTRADIOL 
690 1 0 |a FEMALE 
690 1 0 |a MAMMARY NEOPLASMS, EXPERIMENTAL 
690 1 0 |a MEDROXYPROGESTERONE 17-ACETATE 
690 1 0 |a MICE 
690 1 0 |a MICE, INBRED BALB C 
690 1 0 |a PROGESTINS 
690 1 0 |a RECEPTORS, ESTROGEN 
690 1 0 |a RECEPTORS, PROGESTERONE 
700 1 |a Molinolo, A. 
700 1 |a Lanari, C. 
773 0 |d 1999  |g v. 54  |h pp. 93-99  |k n. 2  |p Breast Cancer Res. Treat.  |x 01676806  |t Breast Cancer Research and Treatment 
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856 4 0 |u https://doi.org/10.1023/A:1006177619192  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_01676806_v54_n2_p93_Montecchia  |y Handle 
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