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Estrogen inhibition of MPA-induced mouse mammary tumor transplants
E Kordon1, C Lanari, A A Molinolo
1Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Abstract:
Estrogen compounds were used to treat mice bearing syngeneic transplants of medroxyprogesterone acetate(MPA)-induced BALB/c mammary adenocarcinomas. Both MPA-dependent and MPA-independent tumor lines were used. These lines expressed estrogen (ER) and progesterone receptors (PR). We demonstrate that different doses of estradiol benzoate (EB) and 17-beta-estradiol (E2) inhibit tumor growth and induce tumor regression in both MPA-independent and -dependent tumors, even in the presence of MPA or progesterone (P). EB was unable to induce regression of (ER-) hormone-independent tumor lines. A few MPA-dependent tumors became resistant to the estrogenic treatment; in subsequent passages some of these tumors retained their MPA-responsiveness, although estrogen sensitivity was not recovered.
Insights
Estrogen therapy effectively inhibited growth and induced regression in mouse mammary tumors expressing estrogen receptors, regardless of progesterone dependency. However, estrogen receptor-negative tumors did not respond, and some tumors developed resistance to estrogen treatment.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Medroxyprogesterone acetate (MPA)-induced mammary adenocarcinomas in BALB/c mice were utilized to study hormone receptor interactions.
- Tumor lines were characterized as either MPA-dependent or MPA-independent, with both expressing estrogen receptors (ER) and progesterone receptors (PR).
Purpose of the Study:
- To investigate the efficacy of estrogen compounds in treating hormone-dependent and independent mammary tumors.
- To determine the role of estrogen receptors (ER) in mediating tumor response to estrogen therapy.
Main Methods:
- Treatment of mice bearing syngeneic mammary adenocarcinoma transplants with varying doses of estradiol benzoate (EB) and 17-beta-estradiol (E2).
- Evaluation of tumor growth inhibition and regression in both MPA-dependent and MPA-independent tumor lines.
- Assessment of tumor response in the presence of MPA or progesterone (P) and in ER-negative tumor lines.
Main Results:
- Estradiol benzoate (EB) and 17-beta-estradiol (E2) demonstrated significant inhibition of tumor growth and induced regression in both MPA-dependent and -independent tumors, even with concurrent MPA or progesterone (P) administration.
- EB was ineffective in inducing regression of estrogen receptor (ER)-negative, hormone-independent tumor lines.
- A subset of MPA-dependent tumors developed resistance to estrogen treatment, with some retaining MPA responsiveness but losing estrogen sensitivity upon subsequent passages.
Conclusions:
- Estrogen therapy is a viable strategy for inhibiting growth and inducing regression in ER-positive mammary tumors, irrespective of progesterone dependency.
- Estrogen receptor (ER) expression is critical for mediating the anti-tumor effects of estrogen compounds.
- Tumor resistance to estrogen therapy can emerge, potentially impacting long-term treatment efficacy.