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M Onoda

Publications and source records attributed to M Onoda.

At least 55 records · Page 3Linked to original sources
PubMed1995

A new mitochondrial DNA deletion associated with diabetic amyotrophy, diabetic myoatrophy and diabetic fatty liver.

Mitochondrial dysfunctions of the muscle in diabetic amyotrophy and of the liver in diabetic fatty liver have been reported. We investigated mitochondrial gene mutations in three cases: (1) a patient with diabetic amyotrophy in the muscles of the lower extremities, and neuropathy; (2) 5 diabetics with myoatrophy, diabetic nephropathy, and chronic renal failure; and (3) an IDDM patient with a diabetic fatty liver. We identified a 5778-bp deletion (8214-13991) in mitochondrial DNA from the muscle and liver biopsy specimens by the primer shift PCR and PCR-direct sequence methods. It is speculated that 5778-bp deletion is due to homogeneous recombination in the 7-bp repeat sequence of TCCTAGA flanking the region deleted in the mitochondrial DNA. Determination of respiratory chain enzyme activities in fresh muscle mitochondria demonstrated the defect in complex I activity. The deletion covers areas coding ND3, ND4, ND4L, and ND5 in complex I. The 5778-bp deletion might cause a defect in mitochondrial oxidative phosphorylation and contribute to the pathogenesis of diabetic amyotrophy, myoatrophy with diabetic nephropathy, and chronic renal failure, as well as diabetic fatty liver in IDDM.

Adolescent↗
PubMed1995

Chemoprevention by dietary dehydroepiandrosterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats.

When pregnant rats received whole body irradiations with 260 cGy gamma-ray at day 20 of pregnancy, and were then implanted with a diethylstilbestrol (DES) pellet for an experimental period of 1 year under feeding of a control diet, a high incidence (96.2%) of mammary tumors was observed. Administration of dietary 0.6% dehydroepiandrosterone (DHEA) together with DES implantation significantly decreased the incidence (35.0%) of mammary tumors. The first appearance of palpable tumors in the DHEA-fed group was 4.5 months later than that in the control group. For clarification of the mechanism of the chemopreventive action, we measured hormone levels in the serum of DHEA-fed rats. In the DHEA diet rats, the concentration of estradiol-17 beta exceeded, by approximately 6-fold, that in the control rats, while the levels of progesterone and prolactin were decreased by 30 and 45%, respectively. Interestingly, DHEA feeding prevented DES-induced hypertrophy of pituitary glands and DES-induced high level of prolactin in pituitary glands detected by immunohistochemical studies, but stimulated the development of mammary glands more than that in control rats treated with DES alone. These findings suggest that DHEA has a potent preventive activity against the promotion/progression phase of radiation-induced mammary tumorigenesis. The mechanism of chemoprevention by change of endocrinological environment is discussed.

Animals↗
PubMed1995

Ventricular gradient variability. New ECG method for detection of ischemic heart disease.

The usefulness of ventricular gradient variability for detecting the presence of ischemic heart disease was evaluated in 38 patients with coronary artery disease (group 1), 21 patients with chest pain and no coronary artery disease (group 2), and 33 healthy control subjects. The ventricular gradient of each consecutive heartbeat at rest over a 22-second interval was calculated using a microcomputer. The SD and coefficient of variation for azimuth, elevation, and magnitude were used as indices of ventricular gradient variability. The SD and coefficient of variation of both the magnitude and elevation of ventricular gradient in group 1 were significantly greater than those of the other two groups (P < .01, respectively). When the normal upper limit was defined as 2SD above the mean value in the control group, a comparison between the findings for group 1 and group 2 revealed that the coefficient of variation of magnitude of the ventricular gradient was the most sensitive (82%) and specific (91%) index for coronary artery disease (chi-square test, P < .001). This study suggests that the variability in the magnitude of the ventricular gradient is a reliable index of ischemic heart disease.

Electrocardiography↗
PubMed1995

Estradiol-17 beta as an initiation modifier for radiation-induced mammary tumorigenesis of rats ovariectomized before puberty.

This investigation evaluated the roles of estradiol-17 beta, progesterone and prolactin in the initiation of mammary tumorigenesis by irradiation. Sixty day old Wistar-MS rats ovariectomized bilaterally at 23 days of age were injected daily with olive oil, estradiol-3-benzoate (E2B), progesterone or haloperidol for 14 days, and were then irradiated with gamma-rays (260 cGy) on the morning following the last injection. Diethylstilbestrol pellets were administered by implantation 30 days after the irradiation. Following treatment with E2B, the incidence of mammary tumors was increased 2.2-fold, in comparison with that in the corresponding control rats. Bilateral ovariectomy before puberty caused the mammary glands of adult rats to atrophy, and a low degree of differentiation with long narrow ducts was observed in whole mounts. The DNA synthesis in the mammary glands and serum prolactin level of E2B-treated rats were markedly increased and the terminal ducts showed distinctly increased differentiation into terminal end buds and alveolar buds with prolactin receptors. When progesterone, another ovarian hormone, or haloperidol, a dopamine antagonist in adenohypophysis, was injected into the rats under estrogen-free conditions, neither expression of prolactin receptors nor stimulation of DNA synthesis was observed in the mammary glands, and the incidence of mammary tumors induced by irradiation was lower than that observed in rats treated with E2B. Combined treatment with E2B and progesterone resulted in a reduction in the incidence of mammary tumors and in serum prolactin levels compared with those in E2B alone, in spite of the synergistic effects on prolactin receptor concentration and DNA synthesis by the two hormones. On the other hand, concurrent administration of haloperidol did not reduce the E2B-induced tumor incidence or prolactin concentration in serum. Many of the mammary tumors which developed in the ovariectomized rats were of the ER(-)PgR(-) type. The incidence of development of ER(+)PgR(+) tumors was increased by treatment with E2B before the irradiation, and no ER(-)PgR(-) tumors were observed in this group. Our results suggest that estrogen is a direct or indirect sensitizer for tumor initiation by radiation, and is also one of the regulatory factors for hormone dependence of radiation-induced mammary tumors.

Animals↗
PubMed1994

Pancreatic beta-cell secretory defect associated with mitochondrial point mutation of the tRNA(LEU(UUR)) gene: a study in seven families with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS).

Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNA(LEU(UUR)) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Postnatal expression of nerve growth factor receptors in the rat testis.

Because nerve growth factor beta (NGF beta) and its corresponding receptors have been implicated in the paracrine regulation of spermatogenesis, we examined the postnatal developmental expression of the low- and high-affinity NGF receptors in the rat testis, and localized their expression to specific testicular cell types. The neurotropin receptors consist of a low-affinity p75 nerve growth factor receptor (LNGFR) and a family of high-affinity tyrosine receptor kinases (trk). Both the p75 LNGFR gene product and the trk receptor gene product were detected in immature rat testes, with maximal expression in 10- and 20-day-old rats. Expression of the testicular p75 LNGFR and the trk receptor progressively declined in older animals so that they were barely detectable in 90-day-old adult rats. The 75-kDa LNGFR was detected in membrane fractions of Sertoli cells, whereas the p75 LNGFR was not detected by Western blot in membrane fractions of round spermatids and primary spermatocytes. Interestingly, microsomal fractions of peritubular myoid cells were immunoreactive for a 65-kDa band on Western blots with the p75 LNGFR monoclonal antibody. Immunoblot analysis of the trk receptor in cell lysates of isolated cell types was inconclusive. Excess NGF beta and round spermatid protein, which is known to contain a NGF-like protein, were both capable of displacing the binding of 125I-NGF beta from the surface of Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Modulation of transferrin secretion by epidermal growth factor in immature rat Sertoli cells in vitro.

The modulation of transferrin secretion by FSH and epidermal growth factor (EGF) was studied in highly pure, primary cultures of immature rat Sertoli cells grown on a reconstituted basement membrane (Matrigel) in bicameral chambers. Sertoli cell purity was assessed by (1) morphometry, (2) alkaline phosphatase cytochemistry (a specific marker enzyme for peritubular cells) and (3) immunocytochemistry for the alpha-isoform of smooth muscle actin in contaminating peritubular cells. Results revealed a less than 0.5% peritubular cell contamination. During initial periods of culture with EGF or FSH alone or in combination, both EGF and FSH alone maintained transferrin secretion over basal values and their effects were additive. At subsequent times, EGF alone maintained transferrin secretion, but to less extent than did FSH alone, and inhibited significantly the ability of FSH to maintain transferrin secretion. The ratio of polarized transferrin secretion in response to FSH, EGF, or in combination was also examined. FSH significantly reversed the polarity of transferrin secretion, whereas EGF, although significantly reducing the ratio of apical to basal transferrin secretion, did not lead to a preferential basal secretion of transferrin. The change in the apical:basal transferrin secretion ratio, however, was not due to a reversal of the apically secreted transferrin towards a basal direction, but rather to an increase in the total basally secreted transferrin. The effects of cell density effects on transferrin secretion were then examined. At low cell density, the relative ability of EGF and FSH together to maintain transferrin secretion was greater than at high cell density, but overall transferrin secretion was greater as cell density increased. The inhibition of FSH by EGF on transferrin secretion was also density dependent: EGF significantly inhibited FSH effects at low cell density, but failed to do so at high cell density. These results suggest that regulation of transferrin secretion by Sertoli cells appears to be under dual control, involving both FSH and EGF and may provide an explanation for the mechanism by which EGF exerts a regulatory role in spermatogenesis.

Animals↗
PubMed1994

Diabetes with mitochondrial gene tRNALYS mutation.

OBJECTIVE: To solve a possible relationship between mtDNA mutation of tRNALYS(8344) and diabetes, we have surveyed the tRNALYS mutation, glucose intolerance, and insulin secretory capacity in a Japanese family with diabetes and myoclonic epilepsy with ragged-red fiber disease. Several lines of evidence suggested possible linkage between mtDNA mutation and diabetes (1-4). RESEARCH DESIGN AND METHODS: DNA was isolated from peripheral lymphocytes. The polymerase chain reaction analysis for the tRNA(LYS)(8344) mutation of the mtDNA was conducted as described by Larsson (5). Insulin secretory capacity was assessed by 24-h urinary C-peptide immunoreactivity response (CPR) excretion and plasma CPR to glucagon administration. RESULTS: We identified seven subjects with the tRNA(LYS) mutation as well as seven non-mutated members in the pedigrees. Oral glucose tolerance tests in the pedigree indicated that five of the mutated subjects were diabetic, one had impaired glucose tolerance, and one had normal glucose tolerance (NGT), whereas all nonmutated family members had NGT. The pedigree shows maternal transmission of diabetes and the tRNA(LYS) mutation over three generations. Twenty-four-hour urinary excretion of CPR was significantly reduced in the mutant subjects (mean +/- SD, 67.8 +/- 79.2 nmol/day, n = 6, P < 0.001) compared with the nonmutant members (276.6 +/- 41.8 nmol/day, n = 5) and the age-matched normal control subjects (263 +/- 64.3 nmol/day, n = 12). Plasma CPR 6 min after glucagon injection demonstrated a marked reduction in the mutant subjects (3.68 +/- 3.45 nmol/l, n = 5, P < 0.001) compared with the nonmutant members (19.4 +/- 1.17 nmol/l, n = 5) and the normal control subjects (15.8 +/- 3.81 nmol/l, n = 12). Bilateral neurosensory deafness was demonstrated in five of seven (71.4%) mutant subjects (five of five [100%] mutated diabetic patients), but not detected in six nonmutant members. CONCLUSIONS: This observation is the first report of association of diabetes with the mitochondrial tRNA(LYS) mutation. Insulin secretory capacity was significantly lower in the mutant members than in the nonmutated members. These findings suggest that the pancreatic beta-cell secretory defect of insulin might be one of the phenotypes of the mitochondrial tRNA(LYS) mutation.

Adult↗
PubMed1994

Urinary chiro-inositol excretion is an index marker of insulin sensitivity in Japanese type II diabetes.

OBJECTIVE: To determine the relationship between urinary chiro-inositol excretion and insulin sensitivity in Japanese type II diabetic patients. RESEARCH DESIGN AND METHODS: Eighteen subjects were age-matched, nonobese, type II diabetic patients. Eight subjects had impaired glucose tolerance (IGT), and 10 had normal glucose tolerance (NGT). We quantified urinary chiro-inositol excretion using gas chromatography-mass spectrometry and the insulin sensitivity index (SI), and glucose effectiveness (SG) using Bergman's modified minimal model method. RESULTS: The urinary excretion of chiro-inositol was much lower in the diabetic patients (32.3 +/- 16.0 mumol/day, means +/- SD) than in the NGT subjects (96.0 +/- 17.6; P < 0.0001) and IGT subjects (58.9 +/- 11.6; P < 0.0001). SI was much lower in the diabetic patients (3.81 +/- 1.49) than in the NGT subjects 6.30 +/- 1.59, P < 0.0005). SG was much lower in the diabetic patients (2.14 +/- 0.56) than in the NGT subjects (3.07 +/- 0.38, P < 0.0001). There was a significant correlation between urinary chiro-inositol excretion and SI (r = 0.766), as well as a significant correlation between urinary chiro-inositol excretion and SG (r = 0.747).

Diabetes Mellitus, Type 2↗
PubMed1993

A 24,500 Da protein derived from rat germ cells is associated with sertoli cell secretory function.

A function and identify of a 24,500 Da protein derived from round spermatids of the rat testis was investigated with a specific polyclonal antiserum raised against RSP-24.5. The proteins released from cultured round spermatids significantly stimulated the secretion of de novo synthesized protein from cultured immature rat Sertoli cells 2.4-fold above control levels. Immunoprecipitation of RSP-24.5 from round spermatid protein further enhanced the stimulation of Sertoli cell protein secretion up to 3.1-fold above control levels, indicating that RSP-24.5 plays a role in the down regulation of Sertoli cell secretion. The antiserum recognized the 24,500 Da protein in Western blots of round spermatid protein, pachytene spermatoctye protein, Sertoli cell lysate and peritubular myoid cell lysate. A 40 amino acid sequence of a cyanogen bromide cleaved internal fragment of RSP-24.5 showed 80.5% homology to a phosphatidylethanolamine binding protein. These results suggest that phosphatidylethanolamine binding protein participates in the negative regulation of Sertoli cell secretory function during spermatogenesis.

Amino Acid Sequence↗
PubMed1993

Chemotaxis and chemokinesis of human prostate tumor cell lines in response to human prostate stromal cell secretory proteins containing a nerve growth factor-like protein.

The migration of three human prostate tumor epithelial cell lines (TSU-pr1, PC-3, DU-145) in response to secreted protein from a human prostate stromal cell line was investigated by using the modified blind-well Boyden chamber assay. Migrated cells were quantified by spectrophotometrically measuring the concentration of crystal violet stain extracted from their nuclei. Cell number was correlated linearly with the concentration of extracted crystal violet stain. All three tumor cell lines showed intrinsic migratory ability in the absence of chemoattractants, such that approximately 1-7% of plated cells migrated across the filter of the Boyden chambers during a 5-h incubation period. Prostate tumor cell migration was significantly enhanced (3-13-fold) in response to stromal cell secretory protein in a dose-dependent manner, whereas bovine serum albumin had no effect on stimulating tumor cell migration. Immunoprecipitation of the stromal cell secreted protein with a nerve growth factor antibody partially and significantly reduced its stimulatory activity for tumor cell migration. A Zigmond-Hirsch matrix assay of tumor cell migration in response to various concentration gradients of stromal cell secreted protein demonstrated both chemotaxis and chemokinesis by all three cell lines. These results are consistent with the stromal cell secretory protein stimulation of chemokinetic tumor cell migration through the capsule of the prostate. Outside of the prostate gland metastasis of tumor cells may occur by chemotaxis to preferential sites containing chemoattractants similar to or related to maintenance factors that can substitute for components of stromal cell secretory protein.

Carrier Proteins↗
PubMed1993

Stromal-epithelial paracrine interactions in the neoplastic rat and human prostate.

Homotypic paracrine interactions in the rat and human prostate have been investigated using prostatic stromal cells and neoplastic epithelial cells (PA-III, rat; TSU-pr1, human). Secretory proteins prepared from each cell type were used to determine the dose dependent regulation of growth (DNA synthesis) of the corresponding homotypic responder cell, as determined by 3H-thymidine incorporation. PA-III secretory protein stimulated rat stromal cell proliferation by 1.8-fold. This stimulatory activity of PA-III protein on stromal cell proliferation was partially reduced (approximately 35%) by treatment with nerve growth factor (NGF) antibody, whereas neither acidic fibroblast growth factor (aFGF) antibody nor basic fibroblast growth factor (bFGF) antibody immunoneutralized the stimulatory activity of PA-III cell protein. In the corresponding opposite interaction, rat stromal cell protein modulated PA-III growth in a biphasic manner. At lower concentrations of stromal cell protein (1.25 micrograms/ml) PA-III cell growth was stimulated by 1.6-fold, whereas at higher concentrations of protein (100 micrograms/ml) PA-III cell growth was inhibited to 60%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with NGF antibody reduced PA-III cell relative growth to approximately 30% and 5%, respectively. bFGF antibody treatment of stromal cell protein at 1.25 micrograms/ml did not influence relative growth, whereas bFGF antibody treatment of 100 micrograms/ml stromal cell protein reduced relative growth by an additional 40%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with aFGF antibodies reduced relative growth from that observed at these two protein concentrations by approximately 50% in both cases. Human epithelial TSU-pr1 protein stimulated human stromal cell proliferation approximately 1.7-fold. Treatment of TSU-pr1 protein with NGF antibody resulted in stimulation of human stromal cell proliferation (4-fold). In the corresponding opposite interaction, human stromal cell secretory protein stimulated TSU-pr1 epithelial cell proliferation in a dose-dependent manner up to a maximum of 2.6-fold. This stimulation of TSU-pr1 proliferation by stromal cell secretory protein was reduced to 20% of maximal levels by treatment with antibody against NGF, whereas antibodies against bFGF and aFGF did not significantly influence the stimulatory effect of stromal cell secretory protein mediated proliferation of TSU-pr1 cells. These results suggest that prostatic stromal cells and neoplastic epithelial cells secrete several paracrine factors. One of these factors is nerve growth factor-like, and appears to have a major non-neurotrophic influence on the paracrine regulation of prostatic growth.

3T3 Cells↗
PubMed1993

A 29,000 M(r) protein derived from round spermatids regulates Sertoli cell secretion.

Within the last decade it has become accepted that germ cells can modulate Sertoli cell function in a paracrine interactive manner during the regulation of spermatogenesis. In this context, we undertook to identify a specific factor in round spermatid conditioned media that could stimulate Sertoli cell secretory function. Rat round spermatids isolated by centrifugal elutriation were cultured and the concentrated conditioned media were fractionated by Sephacryl S-200 gel filtration column chromatography. The biological activity of the fractionated round spermatid protein was assessed as stimulation of total protein and transferrin secretion from Sertoli cells that had been isolated from 18-day-old immature rat testes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the gel-filtration fractions showed two predominant proteins of 29,000 and 24,500 molecular weight which coexisted in the fractions containing the greatest biological activity. These two proteins were transferred to a nitrocellulose membrane and excised to raise polyclonal antibodies. Western blot analysis of the 29,000 M(r) protein demonstrated that it specifically occurred in round spermatid conditioned media, whereas no immunoreactive band was observed in either the conditioned media or cell lysates of other testicular cell types such as primary spermatocytes, Sertoli cells and peritubular myoid cells. Following subcellular fractionation of round spermatids by differential centrifugation, the 29,000 M(r) protein was detected by Western blots specifically in the cytosolic fraction of round spermatids, and was absent from the nuclear, mitochondrial, lysosomal and microsomal fractions. The antibody did recognize a few higher molecular bands in the cytosolic fraction which may represent precursor forms of the 29,000 M(r) protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Incidence of acetylcholine-induced spasm of coronary arteries subjected to balloon angioplasty.

To examine the vasospastic activity of coronary arteries which have been subjected to previous balloon angioplasty, we conducted an acetylcholine provocative test at diagnostic catheterization in 147 consecutive patients. All patients underwent successful elective angioplasty and had follow-up angiography 1 to 6 months after the procedure. Sixty-two patients had a history of prior myocardial infarction and 43 patients had multivessel coronary artery disease. Angioplasty was performed on 176 vessels. Incremental doses of acetylcholine (25 micrograms, 50 micrograms, 100 micrograms) were injected into the right and left coronary arteries over a period of 1 min. The incidence of coronary spasm of arteries which had been subjected to angioplasty was 44%. Angiographic restenosis was observed in 59 patients (40%). There was no correlation between the occurrence of coronary spasm and the presence of restenosis. The maximal dose of injected acetylcholine was smaller in patients with positive evidence of spasm than in patients with negative evidence of spasm (55 +/- 27 micrograms vs 82 +/- 28 micrograms, p < 0.01). In patients with single vessel coronary artery disease, the incidence of spasm of the contralateral artery, i.e. the artery without angioplasty, was lower than that of the artery subjected to angioplasty (22% vs 46%, p < 0.01). Thus, the data suggest that coronary arteries which have been previously subjected to angioplasty have enhanced vasospastic activity in response to acetylcholine.

Acetylcholine↗
PubMed1993

Developmental expression of GTP-binding proteins in rat testes.

The expression of guanine nucleotide-binding proteins (G proteins) during the development of rat testes was investigated. Immunohistochemical studies on frozen sections and isolated testicular cells demonstrated that the expression of the GTP-binding proteins was developmentally regulated and specific for different cell types. The alpha subunit of the cholera toxin-sensitive stimulatory G protein (Gs alpha) was first detected in testes from 7-day-old rats; its value reached a maximum at 23 days and then decreased to very low or undetectable amounts in testes of 45-day-old and adult rats (60-90 days of age). The Gs alpha subunit appears to be expressed by Sertoli, peritubular myoid and interstitial cells. The common beta subunit (G beta) was present at all ages during development and was more prominent around the periphery of the tubules in younger animals but then became more evident in the cytoplasm of germ cells with increasing age. The pertussis toxin-sensitive inhibitory G proteins, Gi1/2 and Gi3, showed a similar pattern of expression. Sertoli cells and peritubular cells expressed Gi1/2 and Gi3 at very low levels at all ages, whereas pachytene spermatocytes and round spermatids expressed the inhibitory binding proteins only at later ages of development (45-day-old and adult testis). Northern blot analysis showed that with increasing age the Gs alpha mRNA in the testis decreased and this was confirmed by in situ hybridization. These latter studies showed localization of the transcripts to somatic cells but not to germ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Reduced expression of the low affinity nerve growth factor receptor in benign and malignant human prostate tissue and loss of expression in four human metastatic prostate tumor cell lines.

In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has been shown to participate in paracrine mediated growth of a human tumor epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues, and four metastatic tumor cell lines of the human prostate. In primary epithelial cell cultures of normal human prostate the p75 NGF-R was localized by immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis of the NGF-R in subcellular fractions of normal prostate tissue identified an M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However, microsomal preparations of five prostatic adenocarcinoma and five benign prostatic hyperplasia specimens showed varying immunoreactivity among samples, all of which expressed less of the p75 NGF-R than the normal tissue. Interestingly, microsomal preparations of the human prostatic epithelial cell lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate tissue, partial loss of NGF-R expression in benign and malignant prostate tissue, and complete loss of NGF-R expression in the four metastatic tumor cell lines, suggests an inverse association of p75 NGF-R expression with the neoplastic progression of the human prostate.

Adenocarcinoma↗