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Estrogen receptor isoforms and progestin hormone dependence in a mouse mammary tumor model
Author(s) -
Actis Andrea M.,
Caruso Silvana P.,
Levin Emanuel
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580509
Subject(s) - tamoxifen , receptor , estrogen receptor , gene isoform , medicine , estrogen , endocrinology , progestin , medroxyprogesterone acetate , antiestrogen , biology , progesterone receptor , carcinogenesis , hormone , mammary tumor , mammary gland , hormone receptor , chemistry , cancer , breast cancer , biochemistry , gene
The close interaction between receptors and other transcription factors suggests that their corresponding transducing signals can trigger functional and structural changes in other related molecules. The effect of a progestinic agent, medroxyprogesterone acetate (MPA), on some of the estrogen‐receptor (ER) parameters was studied in 2 murine mammary tumor sublines with different progestine hormone dependence for their respective growth. The relative binding affinity of estradiol and tamoxifen for the ER, the receptor content and the ER isoforms studied by HPLC were determined in the hormone‐autonomous (HA) and the hormone‐dependent (HD) tumor sublines. In the HA subline administration of MPA did not modify the tumor growth rate, whereas this was accelerated in the HD subline. The ER content was clearly increased in the HD tumor subline, but not in the HA subline, compared with the untreated controls. In contrast, the E, and tamoxifen relative binding affinity far the ER and the isoform profiles were affected by MPA treatment in the HA, but not in the HD tumor subline. The functional change (decrease in relative binding affinity) can be attributed to the appearance of a lower‐molecular‐size ER isoform under the progestinic treatment. Modifications in one receptor molecule by the action of ligands corresponding to another type of receptor show the interconection between transcription factors and the necessity of broadening conventional concepts regarding hormone dependence in mammary tumorigenesis.