Estrogen receptor profiles: changes in mouse and rat mammary tumors by treatment with selective estrogen receptor modifiers

ABSTRACT

The aim of this work was to analyze the effect of estradiol [E2], 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 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, E2, Tam or Ral and NMU-treated rats were analyzed and compared to that of control. The tumor conformer profiles were as follows control and MPA-treated mice showed only one peak [oligomeric form]; E2-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]. 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