Changes in characteristics of human hormone-responsive cancer from hormone-dependent to hormone-independent phenotype in vitro and invivo

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A major problem in the treatment of hormone-dependent tumor concerns the fact that the hormone responsive cancer cells result in alterations in their responses to hormones during the course of endocrine therapy, leading the cancer patients to death with wide-spread metastasis and local extension. Understanding of the changes in characteristics of the cancer cells that progress from hormone-dependent to hormone-independent phenotype both in vitro and in vivo is main concern of the experiments.Growth of androgen-resonsive HONDA human prostatic carcinoma cells was demonstrated in serum-free defined medium formulated with phenol red free RPMI640 supplemented with transferrin 5mug/ml, sodium selenite 3.9ng/ml, phosphoethanolamine 6.1mug/ml, epidermal growth factor 10ng/ml, insulin 5mug/ml, hydrocortisone 51ng/ml and bovine pituitary extract 30mug/ml with or without dihydrotestosterone 2x10^<-9>M. Growth of the cells was highly seedーdensity dependent. Conditioned medium of the cells promoted … More the growth and attachment of the cells. However, supplementation of dihydrotestosterone at the final concentrations of 10^<-8>M to 10^<-11>M strongly inhibited the DNA synthesis of the cell line. Loss of androgen-dependent cellular processes was observed immediately after cell dissociation procedure with enzyme collagenase. In organ culture system of rat ventral prostate, testosterone and its 5 metabolites stimulated RNA and protein synthesis at the concentration of 10^<-6>to 10^<-8>M. Both castration and administration of anti-androgen, chlormadinone acetate, reduced the growth of the original tumor. However, reduction rate in weight of accessory sex organ of the host mice surpassed the growth rate of the tumor, which continued to grow even under successive treatment with antiーandrogen. These results indicate that the androgen-dependent human prostatic cancer cells are fundamentally consisted of hormone-independent phenotype which might embellish with horormonedependent phenotype that needs some tissue integrity for the expression of functional characteristics of its own. Less