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Estrogen receptor profiles: changes in mouse and rat mammary tumors by treatment with selective estrogen receptor
A M Actis1, C M Cocca, A Gutierrez
1Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Objective:
The aim of this work was to analyze the effect of estradiol (E(2)), medroxyprogesterone and the two selective estrogen receptor modulators (SERMs) (tamoxifen (Tam) and raloxifene (Ral)) on the estrogen receptor (ER) conformers profile performed by size exclusion HPLC in relation to hormone dependence of mammary tumors.
Materials And Methods:
Two types of mammary tumors were studied: tumors transplanted in BALB/c mice that are medroxyprogesterone acetate (MPA)-dependent for growth, and tumors induced in Sprague-Dawley rats by intraperitoneal injection of N-nitroso-N-methylurea (NMU). Tumors from mice treated with MPA, E(2), Tam or Ral and NMU-treated rats were analyzed and compared to that of control.
Results:
The tumor conformer profiles were as follows: control and MPA-treated mice showed only one peak (oligomeric form); E(2)-treated mice also showed only one peak (dimer); Tam-treated mice showed one peak corresponding to a possible proteolytic fragment, and Ral-treated mice showed two peaks (oligomeric and a possible proteolytic fragment). On the other hand, NMU-induced mammary tumors from rats showed three peaks (oligomeric, monomeric and proteolytic).
Conclusion:
Our findings may indicate that SERMs affect the aggregation state of ER and thereby its ability to modulate genomic transcription mechanisms related to growth rate.
Insights
Selective estrogen receptor modulators (SERMs) alter estrogen receptor (ER) aggregation states, influencing mammary tumor growth. This study examined ER conformers in hormone-dependent and NMU-induced tumors.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Estrogen receptor (ER) conformation influences mammary tumor growth.
- Selective estrogen receptor modulators (SERMs) are critical in hormone-dependent breast cancer therapy.
Purpose of the Study:
- To investigate the impact of estradiol (E(2)), medroxyprogesterone, and SERMs (tamoxifen, raloxifene) on ER conformer profiles.
- To correlate ER conformer profiles with hormone dependence in mammary tumors.
Main Methods:
- Analysis of ER conformer profiles using size exclusion High-Performance Liquid Chromatography (HPLC).
- Study of medroxyprogesterone acetate (MPA)-dependent mouse mammary tumors and N-nitroso-N-methylurea (NMU)-induced rat mammary tumors.
- Comparison of tumor profiles from control and hormone/SERM-treated animals.
Main Results:
- MPA-treated and control mouse tumors exhibited a single oligomeric ER peak.
- Estradiol (E(2)) treatment resulted in a single dimeric ER peak.
- Tamoxifen (Tam) and Raloxifene (Ral) treatments induced changes in ER conformer profiles, including potential proteolytic fragments.
- NMU-induced rat tumors displayed a more complex profile with oligomeric, monomeric, and proteolytic ER forms.
Conclusions:
- SERMs appear to modulate ER aggregation states.
- Changes in ER aggregation may affect its transcriptional activity and influence mammary tumor growth rates.
