A cell line derived from the androgen-responsive Shionogi 115 mouse mammary carcinoma is being used to investigate the changes in cell function accompanying steroid removal from steroid-responsive breast tumor cells. Shionogi 115 mouse mammary carcinoma cells become androgen unresponsive after two weeks of culture in the absence of testosterone although androgen receptors are still present in the cytoplasm and nucleus. Androgen-responsive cells are fibroblastic in appearance, have a low serum requirement, and can proliferate in suspension culture. Unresponsive cells, however, show a flattened morphology, are serum sensitive, and are anchorage dependent. As the androgen receptor mechanism of the unresponsive cells is intact, loss of sensitivity may be caused by a postreceptor defect. To determine the nature of this defect, the temporal relationships of changes in hormone responsiveness, morphology, serum sensitivity, and growth properties have been examined over a period of seven weeks following removal of testosterone from Shionogi 115 mouse mammary carcinoma cell cultures. Responses to testosterone and anchorage independence are both lost over a period of one to two weeks while serum sensitivity increases more slowly during the same period. The most rapid and least reversible change is seen in morphology. It is suggested that hormone responsiveness is related to properties of the cytoskeleton and cell membrane which influence growth rates and multiple sensitivities of tumor cells.

https://cancerres.aacrjournals.org/content/canres/41/1/258.full.pdf

Correlation of growth properties and morphology with hormone responsiveness of mammary tumor cells in culture.

The estrogen agonist and antagonist activities of eight structurally related synthetic compounds [trans-l-(4β-dimethylaminoethoxyphenyl) l,2-diphenylbut-l-ene (tamoxifen) cis-1- (4β-dimethylaminoethoxyphenyl) 1,2-diphenylbut-l-ene (ICI 47,699), α-(4-pyrrolidinoethoxy)phenyl-4-methoxy-α-nitrostilbene (CI 628), a-(4-dimethylaminopropoxy)phenyl-4-methoxy- a-nitrostilbene citrate (CI 680), l-(2-[p-(3,4-dihydro-6-methoxy- 2-pheny1-1-naphthyl)phenoxy]ethyl)pyrrolidine hydrochloride (nafoxidine), cis(3-[p-1,2,3,4-tetrahydro-6-methoxy-2- pheny1-1-naphthyl)phenoxy]l,2-propanediol (U 23,469) trans-1- (p-β-diethy laminoethoxyphenyl) 1,2- diphenyl - 2 - chloroethylene monocitrate (enclomiphene), and cts-l-(p-β-diethylaminoethoxyphenyl) l,2-diphenyl-2-chloroethylene monocitrate (zuclomiphene)] were tested in the estrogen-withdrawn chick oviduct. No compound demonstrated agonist activity, as assessed by changes in oviduct wet weight, DNA,protein, and progesterone receptor concentration, when administered for 1 or 3 day...

Estrogen antagonists in chick oviduct: antagonist activity of eight synthetic triphenylethylene derivatives and their interactions with cytoplasmic and nuclear estrogen receptors.

B.W. O'malley

Papers

10 – Regulation of Gene Expression in the Eukaryotic Cell