PubMed Health⌕ Search

Biomedical subjects

T C Thompson

Publications and source records attributed to T C Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Growth factors and oncogenes in prostate cancer.

Prostatic cancer is an increasing medical problem. Investigations of the biology of the prostate and the development of prostate cancer have shown that the prostate gland contains high levels of polypeptide growth factors, especially members of the fibroblast growth factor (FGF) and transforming growth factor (TGF)-beta family. Activated oncogenes and elevated proto-oncogene activities including ras and myc have been detected in human prostate cancer tissues, but there is no consensus as to the predominant genetic alterations involved in the progression of this disease. In vivo animal models have shown that relevant growth factors and oncogenes can induce both premalignant and malignant changes in prostate tissue. Additional experimental and clinical studies are needed to present a clearer molecular profile of this important malignancy.

Cell Differentiation↗
PubMed1989

Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ.

ras and myc oncogenes were able to induce distinct phenotypic alterations, resembling different types of premalignant lesions, when introduced into approximately 0.1% of the cells used to reconstitute the mouse prostate gland. While ras induced dysplasia in combination with angiogenesis, myc induced a hyperplasia of the otherwise normally developed organ. ras and myc together induced primarily carcinomas. However, tumor progression was also associated with additional genetic alterations involving gene amplification. Our data indicate that specific types of benign premalignant lesions may reflect the activation of different single oncogenes, and that the consecutive activation of multiple oncogenes could be a causal event in the step-like progression of tumorigenesis.

Animals↗
PubMed1987

Androgen-regulated expression of secretory protein synthesis in mouse ventral prostate.

Two proteins of molecular weights 25 and 12 kDa (p25 and p12 respectively), whose expression is regulated by testosterone, were identified in mouse ventral prostate. An antiserum raised to mouse ventral prostate secretion was used to demonstrate that p25 corresponds to the major secretory glycoprotein in mouse prostatic fluid. This antiserum does not cross-react with the major secretory proteins of the rat ventral prostate. Western blot analysis of mouse ventral prostate proteins using the prostatic secretion antiserum demonstrates that p12 and p25 are detectable at 3 weeks of age, but the maximum level of both proteins is not attained until 5 weeks of age. In addition, synthesis of p25 was also observed in prostate tissue derived from differentiated embryonic urogenital sinus tissue growing as implants under the renal capsule of syngeneic male hosts.

Animals↗
PubMed1986

Androgen-induced biochemical responses in epithelium lacking androgen receptors: characterization of androgen receptors in the mesenchymal derivative of urogenital sinus.

Heterotypic tissue recombinants, composed of adult bladder epithelium obtained from testicular feminization syndrome mice (TfmBLE) and embryonic wild-type rat urogenital sinus mesenchyme (UGM) were grown as subcapsular renal grafts in male athymic nude mice for 30 days. The resultant prostatic tissue that developed was subjected to extensive biochemical analyses for androgen receptors. From previous autoradiographic studies it was shown that UGM possesses androgen receptors and induces the TfmBLE to form prostatic ductal-acinar epithelium that lacks androgen receptors. The purpose of the present study is to biochemically characterize the mesenchymal androgen receptors. According to results obtained by autoradiographic analyses, androgen receptors are expressed in the mesenchyme of tissue recombinants. Cytosolic androgen receptors analyzed by the Scatchard method utilizing R-1881 as a ligand showed that the dissociation constant (Kd) of androgen receptors localized within the mesenchyme of the tissue recombinants differs from that found in the mouse prostate gland, but resembles that found in the rat ventral prostate (VP). Sucrose density gradient analysis of the cytosol androgen receptors showed the presence of 8 S [3H]dihydrotestosterone (DHT) binding component under the low salt condition. The mesenchymal androgen receptors are capable of translocating efficiently from cytosol to nuclear compartment, seemingly unaffected by adjacent TfmBLE. The quantity of both cytosol and nuclear androgen receptors expressed in tissue recombinants is only about 1/3 of that found in the rat VP and is in agreement with the morphometric analysis of tissue recombinants, which indicated that about 1/3 of the cells in the tissue recombinants are stromal cells. These results extend previous autoradiographic results and further suggest that androgen receptors present in the mesenchymal compartment may be necessary for the expression of androgen-elicited responses in the TfmBLE that lacks androgen receptors. In addition, this study confirms a novel model system for the study of mesenchymal androgen receptors in tissues unmolested by mechanical or enzymatic dissociation.

Androgen-Insensitivity Syndrome↗
PubMed1986

Regulation of overgrowth and expression of prostatic binding protein in rat chimeric prostate gland.

Enlargement of the chimeric ventral prostate gland (VP) was induced by directly implanting either fetal urogenital sinus mesenchyme (UGM) or intact fetal urogenital sinus (UGS) into the VP of intact adult rats. The macromolecular content in the chimeric prostate increased from 40-100% (UGM implants) to 200-300% (UGS implants) above control levels. The enlargement of the prostate gland was the result of growth from both the donor tissue and the host gland. Growth of the donor fetal UGS within the host prostate gland may account for the difference observed between the growth induced by fetal UGS and fetal UGM implants. Because fetal UGM regressed when implanted and grown under the renal capsules, the observation of growth in the adult rat VP induced by fetal UGM, either by implanting UGM in situ or forming tissue recombinants of UGM and the adult VP, suggests that fetal UGM requires close association with the VP for the induction of growth to occur. The concentration of an epithelial androgen-dependent protein, the prostatic binding protein (PBP), expressed by the enlarged lobe of the rat VP was similar to that of the control lobe of rat VP. The adult host gland, rather than donor implants, appeared to determine the levels of expression of PBP within the chimeric prostate gland. Immunofluorescence data indicated that PBP was distributed evenly throughout most of the prostatic acini. PBP also accumulated in the lumen of the prostatic acini. Positive immunofluorescence, although less intense, was detected in the UGS remnant, suggesting that fetal UGS was induced by the intact adult VP environment to express PBP. We observed a developmental restriction in the ability of donor prostatic tissues to induce enlargement of the host prostate gland. Fetal UGS was the most effective inducer, whereas neonatal prostatic tissue was marginally effective, and adult prostatic tissue or stromal cells derived from adult VP were completely ineffective.

Androgen-Binding Protein↗
PubMed1984

A new mouse model for prostatic hyperplasia: induction of adult prostatic overgrowth by fetal urogenital sinus implants.

A new mouse model for human BPH has been established. This model was developed on the basis that fetal and adult prostatic cells interact to induce the proliferation of adult prostatic cells. A 10- to 20-fold overgrowth of the adult mouse prostate gland can be induced by implantation of fetal UGS into the adult prostate gland. Components of UGS, fetal UGM, and fetal UGE may be involved in the regulation of adult prostatic overgrowth. The androgen dependency and the specificity (donor tissue, site of implantation, and strain and species) of UGS-induced adult prostatic overgrowth have also been established. The question remains whether the prostatic hyperplasia seen in this mouse model may be representative of human BPH. The observation that fetal UGS implants induce adult prostatic overgrowth in the complete absence of exogenous sex steroids support the hypothesis of McNeal that human BPH may develop as a result of the reactivation of fetal growth potential in the periurethral area of the adult prostate gland. The present mouse model may be used as a test system for the future development of anti-BPH drugs.

Androgens↗
PubMed1984

Extraction of nuclear androgen receptors by sodium molybdate from normal rat prostates and prostatic tumors.

Because sodium molybdate stabilizes steroid receptors, this compound has been included in the homogenizing medium in order to maximize the recovery of measurable steroid receptors in normal and neoplastic tissues. This study demonstrates that sodium molybdate extracts additional androgen receptors from prostatic nuclei in a concentration-dependent manner. Nuclei previously washed with Triton X-100 to remove the outer nuclear membranes released similar numbers of androgen receptors with sodium molybdate as the unwashed nuclei, suggesting that the extracted nuclear androgen receptors are associated with intranuclear matrices. Sucrose density gradient analyses revealed that sodium molybdate-extractable nuclear androgen receptors sedimented similarly to the 0.4 M KCl extract as 4S receptor complexes under high-salt conditions. We have compared the amount of nuclear androgen receptors extracted from normal prostates (ventral prostate and dorsolateral prostate) and Noble hooded rat and Dunning prostatic tumors by a sensitive translocation-extraction procedure. This procedure involves the incubation of minced prostatic tissues, isolated from castrated rats, with [3H]R1881 ( [3H]methyltrienolone; [6,7-3H]-17 beta-hydroxy-17 alpha-methylestra-4,9,11-trien-3-one) at 37 degrees for 2 hr. Crude nuclear pellets were prepared from the minced tissues, and nuclear androgen receptors were extracted with 40 mM Na2MoO4 or 0.4 M KCl. Results showed that the amount of nuclear androgen receptors present in the prostatic tumor nuclei is lower than that found in the normal. Although the percentage of nuclear androgen receptors extracted by sodium molybdate or KCl is similar between androgen-dependent and androgen-independent prostatic tumors, the absolute amounts of nuclear androgen receptors per mg DNA extracted from the former are 2- to 8-fold higher than those found in the latter.

Animals↗
PubMed1983

Epithelial-mesenchymal interactions in prostatic development. II. Biochemical observations of prostatic induction by urogenital sinus mesenchyme in epithelium of the adult rodent urinary bladder.

Adult bladder epithelium (BLE) is induced to differentiate into glandular epithelium after association with urogenital sinus mesenchyme (UGM) and subsequent in vivo growth in syngeneic male hosts. Alteration of epithelial cytodifferentiation is associated with the expression of prostate-specific antigens, histochemical and steroid metabolic activities. These observations suggest that the inductive influence of the UGM has reprogrammed both the morphological and functional characteristics of the urothelium. In this report, differences regarding the mechanisms and effects of androgenic stimulation of prostate and bladder are exploited to determine the extent to which UGM plus BLE recombinants express a prostatelike, androgen-dependent phenotype. Results from cytosolic and autoradiographic binding studies suggest that androgen binding is induced in UGM plus BLE recombinants and that this activity is accounted for by the induced urothelial cells. In UGM plus BLE recombinants, androgen-induced [3H]thymidine or [35S]-methionine uptake analyzed by two-dimensional gel electrophoresis was qualitatively and quantitatively similar to that of prostate as opposed to bladder. These studies indicate that expression within BLE of prostatic phenotype is associated with a loss of urothelial characteristics and that androgen sensitivity is presumably a function of the inductive activities of the stroma.

Animals↗