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


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).


CONCLUSIONS
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.
Actis
A M
AM
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Cocca
C M
CM
Gutierrez
A
A
Croci
M
M
Rivera
E S
ES
Bergoc
R M
RM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008770:Methylnitrosourea; D051379:Mice; D008807:Mice, Inbred BALB C; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D011487:Protein Conformation; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D008770:Methylnitrosourea