Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Changes in profiles of estrogenic receptors in experimental mammary tumors treated with different SERMs

A Actis, CE RiveraRilo, C Cocca, R Bergoc

1 Dept Human Biochemistry, School of Medicine, University of Buenos Aires, and Institute of Health Sciences, Foundation Barcelo, 2 Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina,

To determine differences in profiles of estrogenic receptors' isoforms in relation with hormonedependence. METHODS: We employed two experimental mammary tumor types: 1) Mammary tumors transplanted in BALB/c: one medroxiprogesterone (MPA)-dependent for its growth (C4-HD sub-line) and another non-dependent (BET-HA sub-line); 2) Mammary tumors induced in Sprague-Dawley rats by ip injection of N-Nitroso-N-methylurea (NMU). Tumor-bearing animals were treated with different selective estrogenic receptor modulators (SERMs): Estradiol (E2), tamoxifen (Tam), raloxifen (Ral) and MPA. ER isoforms were determined by high performance liquid chromatography (HPLC) with columns of molecular exclusion Macherey-Nagel Nucleogel GFC 300-8 refrigerated (0-4oC). Fractions were collected each 3 minutes and radioactivity was measured in a liquid scintillography spectrometer. RESULTS: C4-HD sub-line showed only one elution peak belonging to the oligomer form (MW>200kDa); MPA treatment does not modifie the elution profile; treatment with E2, Tam and Ral produced profile modifications: Ral favored the expression of an isoform with lower MW, which may correspond to an ER proteolitic fragment. In the BET-HA sub-line two peaks were showed, one with MW>200kDa (oligomer) and another with MW=110kDa (dimeric isoform). The treatment with MPA produced an increase of the dimeric expression in this sub-line. In tumors NMU ip-induced, the elution profiles were wavering, in accord with the degree of hormone-dependence to estrogen they exhibit. CONCLUSIONS: Obtained results indicate the importance of ER conformation in response to different SERMs. The aggregation state of ER can affect the functionality of them to modulate genome transcription mechanisms.

KEY WORDS: SERMs, mammary tumors, estrogenic receptors, transcription mechanisms.

For more information, contact

Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on synergistic therapies.