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Abstract:

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.

Registro:

Documento: Artículo
Título:Reversal of estrogen-resistance in murine mammary adenocarcinomas
Autor:Montecchia, M.F.; Molinolo, A.; Lanari, C.
Filiación:Lab. of Hormonal Carcinogenesis, Inst. Biologia y Med. Exp. (IBYME), CONICET, Buenos Aires, Argentina
IBYME, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:Estrogens; Hormone independence; Hormone resistance; Mammary adenocarcinomas; Mice; Reversibility; estradiol; estrogen; estrogen receptor; gestagen; hormone receptor; medroxyprogesterone acetate; progesterone receptor; silastic; animal experiment; animal model; article; breast adenocarcinoma; drug resistance; estrogen therapy; estrus cycle; hormone resistance; ligand binding; mouse; nonhuman; priority journal; protein expression; receptor density; receptor down regulation; tumor regression; Adenocarcinoma; Animals; Antineoplastic Agents, Hormonal; Cell Division; Drug Implants; Drug Resistance, Neoplasm; Estradiol; Female; Mammary Neoplasms, Experimental; Medroxyprogesterone 17-Acetate; Mice; Mice, Inbred BALB C; Progestins; Receptors, Estrogen; Receptors, Progesterone
Año:1999
Volumen:54
Número:2
Página de inicio:93
Página de fin:99
DOI: http://dx.doi.org/10.1023/A:1006177619192
Título revista:Breast Cancer Research and Treatment
Título revista abreviado:Breast Cancer Res. Treat.
ISSN:01676806
CODEN:BCTRD
CAS:Antineoplastic Agents, Hormonal; Drug Implants; Estradiol, 50-28-2; Medroxyprogesterone 17-Acetate, 71-58-9; Progestins; Receptors, Estrogen; Receptors, Progesterone
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01676806_v54_n2_p93_Montecchia

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Citas:

---------- APA ----------
Montecchia, M.F., Molinolo, A. & Lanari, C. (1999) . Reversal of estrogen-resistance in murine mammary adenocarcinomas. Breast Cancer Research and Treatment, 54(2), 93-99.
http://dx.doi.org/10.1023/A:1006177619192
---------- CHICAGO ----------
Montecchia, M.F., Molinolo, A., Lanari, C. "Reversal of estrogen-resistance in murine mammary adenocarcinomas" . Breast Cancer Research and Treatment 54, no. 2 (1999) : 93-99.
http://dx.doi.org/10.1023/A:1006177619192
---------- MLA ----------
Montecchia, M.F., Molinolo, A., Lanari, C. "Reversal of estrogen-resistance in murine mammary adenocarcinomas" . Breast Cancer Research and Treatment, vol. 54, no. 2, 1999, pp. 93-99.
http://dx.doi.org/10.1023/A:1006177619192
---------- VANCOUVER ----------
Montecchia, M.F., Molinolo, A., Lanari, C. Reversal of estrogen-resistance in murine mammary adenocarcinomas. Breast Cancer Res. Treat. 1999;54(2):93-99.
http://dx.doi.org/10.1023/A:1006177619192