Previous studies in hereditary and sporadic prostate cancer have indicated the existence of a tumor suppressor gene in chromosomal region 19p13. The BRG1 gene in this region is one of the possible candidates, based on both the frequency of inactivating mutations in human cancer cell lines, including the prostate cancer cell line DU145, and its functional properties. To our knowledge, no studies have been done to evaluate possible involvement of the BRG1 gene in clinical prostate cancer. To accomplish this, we carried out a complete mutation analysis of all 35 BRG1 exons in tumor and constitutional DNA samples from 21 prostate cancer patients. We report the absence of somatic mutations in the panel of samples employed, but the existence of five germline single nucleotide polymorphisms (SNPs) in CpG islands of the BRG1 gene, among them, three novel ones. In conclusion, the study excludes the presence of common BRG1 mutations in prostate cancer.
Although an impressive knowledge has now accumulated concerning the binding of steroid hormones to cytosolic receptors, considerably less is known about the uptake and action of steroids in cell nuclei.During the course of our studies on specific binding of the androgenic steroid [3~]methyltrienolone in human bemgn hjperplastic prostate [ 11, we have investigated the uptake of the steroid by purified nuclei.Since we were unable to obtain steady-state levels of steroid--receptor complexes in the nuclei with time, we decided to study specific uptake of steroids into cells and cell nuclei from various steroiddependent tissues.These studies which are reported below have indicakd a cyclic occurrence of steroidreceptor complexes in prostate, liver and pituitary_ 2. Materials and methods 022 nuclei were prepared from frozen (-70°C) hukmn benign hypeqdastic prostate tissue essentially by the technaque in [2].Human prostate tissue was minced with a pair of scissors and homogefrized with a t&on-glass homogenizer in 5 vol.Tris-HCJ buffer
Due to a combination of aggressive chemotherapy and radical surgery today most cases of advanced non-seminomatous germ cell tumours of the testicle can be cured. The most active chemotherapeutic regimen is a combination of cis-platinum, velban, and bleomycin: the epipodophyllotoxin VP-16-213 still being a second hand alternative. Surgery is applied for definite cure in low-stage disease and for debulking of remaining tumour after initial chemotherapy in advanced stages. Survival figures today are given as 100% in stage I, 90% in stage II, and 60% in stage III. Low-stage seminoma is still routinely treated with radiotherapy, however, chemotherapy seems to markedly improve survival also in advanced stages of this disease. The use of highly toxic chemotherapy and advanced surgery necessitates a concentration of these cases to few centres with experienced staff. The article also briefly discusses classification, symptoms, diagnostic aids, and follow-up procedures.
The characteristics of binding of radiolabeled progesterone, promegestone [17α,21-dimethyl-19-nor-4,9-pregnadiene- 3,20-dione (R5020)], medroxyprogesterone acetate (4- pregnen-6a-methyl-17α-ol-3,20-dione acetate), and methyltrienolone [17β-hydroxy-17α-methyl-4,9,ll-estratriene-3-one (MT)] to the progesterone receptor in human prostatic cytosol have been compared. MT binds to both androgen and progesterone receptors with high affinity (Kd = 0.9 and 0.6 nM, respectively). The binding of MT to the progesterone receptor can be blocked by adding an excess of unlabeled triamcinolone acetonide [9afluoro- llβ,16α,17α,21-tetrahydroxy-l,4-pregnadiene-3,20-dione- 16,17-acetonide (TAC)]. The difference between the binding of [3H] MT in the absence and presence of TAC (i.e. [MT - (MT + TAC)]) represents specific binding of MT to the progesterone receptor. Ligand specificity studies demonstrated that this binding was typical of a progesterone receptor. Furthermore, progesterone receptor levels measured in this way were comparable to those obtained using progesterone, R5020, or medroxyprogesterone acetate as labeled ligands. Progesterone receptor quantitation from the difference MT - (MT + TAC) is of particular advantage when simultaneous quantitation of progesterone and androgen receptors is desired in small tissue specimens, since only three sets of incubations are required: [3H] MT, [3H] MT plus unlabeled TAC, and [3H] MT plus unlabeled MT (to measure nonspecific binding). Conditions are described for the application of this methodology to a microassay. A marked underestimate of progesterone receptor content was observed when incubation was terminated with hydroxylapatite compared to that measured when dextran-coated charcoal was used. The presence of comparable amounts of progesterone and androgen receptors in human prostatic cytosol deserves further investigation. (J Clin Endocrinol Metab55: 1089, 1982)
