bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of high‐affinity receptors for bombesin/gastrin releasing peptide on the human prostate cancer cell lines PC‐3 and DU‐145: Internalization of receptor bound 125I‐(Tyr4) bombesin by tumor cells
Authors: Reile Herta , Armatis Patricia E. , Schally Andrew V. 
Published: February 2007

AbstractSpecific receptors for bombesin/gastrin releasing peptide (GRP) on the androgen‐independent human prostate cancer cell lines PC‐3 and DU‐145 were characterized. No specific binding of 125I‐[Tyr4]‐bombesin to the androgen‐dependent human prostate cancer cell line LNCaP was detectable. The binding of 125I‐[Tyr4]‐bombesin to PC‐3 and DU‐145 cells was found to be time‐ and temperature‐dependent, saturable, and reversible. Scatchard analysis revealed a single class of binding sites with high affinity (Kd 9.8 × 10−11 M for PC‐3, and 9.1 × 10‐11 M for DU‐145 cells at 25°C) and with a binding capacity of 44,000 binding sites/cell and 19,000 binding sites/cell, respectively. Bound 125I‐[Tyr4]‐bombesin was rapidly internalized by PC‐3 cells. The nonhydrolyzable GTP analog GTP‐gamma‐S caused a dose‐dependent inhibition of 125I‐[Tyr4]‐bombesin binding to PC‐3 and DU‐145 cells, indicating that a G‐protein (guanine nucleotide‐binding protein) couples the bombesin receptor to intracellular effector systems. Bombesin and GRP(14‐27) inhibited the binding of 125I‐[Tyr4]‐bombesin to both cell lines in a dose‐dependent manner with inhibition constants (Ki of 0.5 nM and 0.4 nM, respectively. Both cell lines express the bombesin/GRP preferring bombesin receptor subtype, since, in displacement studies, neuromedin B was more than 200 times less potent than bombesin and GRP(14‐27) in inhibiting the binding of 125I‐[Tyr4]‐bombesin. Two synthetic bombesin/GRP antagonists, RC‐3095 and RC‐3110, powerfully inhibited the specific binding of 125I‐[Tyr4]‐bombesin with Ki 0.92 nM and 0.26 nM on PC‐3 cells, and 3.3 nM and 0.89 nM on DU‐145 cells, respectively. These findings indicate that the PC‐3 and DU‐145 human prostate cancer cell lines possess specific high‐affinity receptors for bombesin/GRP, and are suitable models for the evaluation of the antineoplastic activity of new bombesin/GRP antagonists in the treatment of androgen‐independent prostate cancer. © 1994 Wiley‐Liss, Inc.
Antagonism of androgen action in prostate tumor cells by retinoic acid
Authors: Young Charles Y.‐F. , Murtha Patricia E. , Andrews Paul E. , Lindzey Jonathan K. , Tindall Donald J. 
Published: February 2007

AbstractRecent studies have demonstrated that retinoic acid (RA) can repress the growth of human prostatic epithelial cells. Since the proliferation of prostate cells is highly dependent on androgen stimulation, presumably via its cognate receptor, we investigated the effects of RA on the expression of the androgen receptor and other androgen‐regulated genes in the human prostatic adenocarcinoma cell line LNCaP. Using a radioligand binding assay, we found that androgen‐binding activity was reduced 30‐40% in cells treated with 10−5 M RA plus 6 nM dihydrotestosterone (DHT), as compared to cells with the androgen alone. Moreover, the reduction of the androgen receptor (AR) was not accompanied by alteration of the ligand‐binding affinity. Concomitant changes in the function of AR were manifested by a dramatic reduction in AR‐mediated transcription activity in a transfection experiment. Androgen‐induced levels of both prostate‐specific antigen (PSA) and human glandular kallikrein‐1 (hKLK2) mRNAs were significantly repressed by RA in a dose‐ and time‐dependent manner. Consistent with this finding, androgen induction of PSA glyco‐protein was also repressed by RA, with maximal inhibition occuring at 10−5 M. These data suggest that the suppression of proliferation and function of prostatic cells by RA may be via modulatory effects on the AR. © 1994 Wiley‐Liss, Inc.
Biosynthesis and secretion of laminin and S‐laminin by human prostate carcinoma cell lines
Authors: Rabinovitz Isaac , Cress Anne E. , Nagle Ray B. 
Published: February 2007

AbstractLaminin has been previously shown to participate in tumor invasion and metastasis. Tumorigenesis by human prostate cell lines can be influenced by exogenous laminin. We have found that the human prostate tumor cell lines DU145, LNCaP, and PC‐3 produce a variant form of the B1 chain of laminin, known as S‐laminin. DU145 cells produce laminin containing a ratio of A:B1:B2:S of 1.8:1.0:2.5:1.0, respectively, compared to LNCaP cells, which have a ratio of A:B1:B2:S of 1.0:0:10.0:2.5. Kinetic analysis of laminin production showed that LNCaP cells retained most of their laminin production and secreted laminin forms characterized by decreased levels of n‐acetyl glucosamine and sialic acid. In contrast, DU145 cells secreted most of their laminin in mature forms. LNCaP cells bound very little laminin to their surface. These features of LNCaP cells could contribute to their documented low adhesivity in vitro and its nontumorigenic phenotype. © 1994 Wiley‐Liss, Inc.
Bone alkaline phosphatase and prostate‐specific antigen in the monitoring of prostate cancer
Authors: Cooper E. H. , Whelan P. , Purves D. 
Published: February 2007

AbstractA retrospective study has been made on the interrelationship of serum bone alkaline phosphatase (BAP), measured by the Ostase‐RIA, and prostate‐specific antigen (PSA) in 156 patients with M0 and M1 prostate cancer. BAP is a more sensitive and more specific method of determining osteoblast activity than total alkaline phosphatase (TAP). The main difference between these two assays is seen when the TAP is in the range of normal to twice‐normal.BAP shows a low intraindividual variation in M0 disease, and was within normal limits in 18 patients following radical prostatectomy with a PSA < 0.1 ng/ml. A raised BAP was observed in 86.4% of M1 disease at diagnosis before treatment. The change of BAP was concordant with PSA in 69% of 49 cases of M1 disease, although there are marked differences in the rates of change of the two markers. A nadir of PSA ⩽ 10 ng/ml after androgen blockade in M1 disease was associated with a high probability of a normal BAP. © 1994 Wiley‐Liss, Inc.
Molecular and cellular changes associated with the acquisition of metastatic ability by prostatic cancer cells
Authors: Rinker‐Schaeffer Carrie W. , Partin Alan W. , Isaacs William B. , Coffey Donald S. , Isaacs John T. 
Published: February 2007

AbstractPresently, one of every four cancers diagnosed in American males is of prostatic origin. Once prostatic cancer metastasizes, it is a fatal disease for which no therapy presently available is curative. Because of these facts, there is a growing interest in the early detection and screening of men for prostate cancer. Such screening could potentially identify 10 million American men with histological prostatic cancer. It is estimated that approximately 7% (700,000) of these men will eventually die from their disease if left untreated. This raises the critical question of which of the remaining 93% (9,300,000) of men with nonlethal, but potentially life‐altering, histologically detectable prostatic cancer should receive therapy. There is no diagnostic method presently available which allows men with histologically detectable prostatic cancer, whet require immediate therapy, to be distinguished from those requiring either delayed therapy or no treatment. Acquisition of metastatic ability by such histologically detectable prostatic cancer cells is a definitive criterion upon which to base such a diagnostic substaging method. Identification of the cellular and molecular requirements for acquisition of metastatic ability by prostatic cancer cells is needed for the development of such methods. This article will focus on what is known concerning general cellular and specific molecular changes associated with the acquisition of metastatic ability by prostatic cancer cells, and suggested areas for future studies. © 1994 Wiley‐Liss, Inc.
Androgen receptor alterations in prostatic carcinoma
Authors: Klocker Helmut , Culig Zoran , Hobisch Alfred , Cato Andrew C. B. , Bartsch Georg 
Published: February 2007

AbstractIntracellular action of androgens is mediated by the androgen receptor (AR), which is a key element of the androgen signal transduction cascade and a target of endocrine therapy for prostatic carcinoma. Therefore, the qualitative and quantitative alterations of AR expression in prostatic carcinomas and their possible implications for tumor progression and treatment are of great interest. Findings in prostatic tumor cell lines of rat and human origin suggest a reduction of AR protein expression accompanied by an increase in tumor malignancy. However, immunohistochemical studies and binding assays demonstrated presence of ARs in all histological types of prostatic tumors, in therapy‐responsive as well as in therapy‐unresponsive ones. AR content of prostatic tumor specimens did not correlate with outcome of endocrine therapy of advanced prostatic carcinoma in these studies. Solely the degree of heterogeneity of AR expression may be useful as an indicator of responsiveness to therapy. AR mutations have been detected in the LNCaP cell line and in three primary prostatic tumor specimens. Three of them are point mutations in the hormone‐binding domain of the AR, the fourth mutation is a CAG‐microsatellite depression in the N‐terminus. Evidence coming from studies on AR in prostatic cancer highlights the possibility that AR structural alterations may have significance in tumor progression. © 1994 Wiley‐Liss, Inc.
Immunohistochemical localization of estrogen‐specific 17β‐hydroxysteroid oxidoreductase in the human and mouse prostate
Authors: Pylkkänen L. , Santti R. , Salo L. , Mäentausta O. , Vihko R. , Nurmi M. 
Published: February 2007

AbstractThe estrogen‐specific 17β‐hydroxysteroid oxidoreductase (17β‐HSOR) enzyme protein was stained immunohistochemically in the newborn and adult human prostate as well as in the mouse prostate. In the newborn human prostate, ductal and urethral epithelia were faintly stained, whereas in the adult human prostate, intense staining for 17β‐HSOR enzyme antigen could be detected in the epithelium of the collecting ducts and urethral epithelium as well as in the epithelium of the intraprostatic vas deferens and seminal vesicle epithelium. Immunostaining was weak in the prostatic tissues of both newborn and adult prostate. No positive cells were found in stroma. The activity of NADPH‐dependent 3H‐estrone reductase was detectable in cell‐free homogenates prepared from human prostatic tissues. The activities showed a good correlation with immunocytochemical findings.In the mouse, neonatal estrogenization resulted in intensively stained epithelium of the collecting ducts at the age of 14 days. Moreover, when adult control and neonatally estrogenized mice were implanted with 17β‐estradiol, the metaplastic epithelium of the periurethral collecting ducts of neonatally estrogenized mice was intensively stained with 17β‐HSOR. These findings suggest that metaplastic epithelium rises from 17β‐HSOR‐positive cells.The similar distributions of 17β‐HSOR‐positive cells confirm the concept of homology in the posterior estrogen‐responsive periurethral region (containing the periurethral ducts and periurethral glands) of the mouse and humans. Our findings further suggest that the 17β‐HSOR‐positive cells may have the same origin and hormonal control in both species. © 1994 Wiley‐Liss, Inc.
Effects of estrogens and progestogens on the membrane permeability and growth of human prostatic carcinoma cells (PC‐3) in vitro
Authors: Widmark Anders , Henriksson Roger , Bergh Anders , Grankvist Kjell , Damber Jan‐Erik 
Published: February 2007

AbstractThe effects of estrogens and progestogens in the management of prostatic adenocarcinoma are generally believed to be related to their suppressive effect on the hypothalamic‐pituitary‐testicular axis, but other mechanisms have also been suggested. The present study was designed to investigate if an androgen‐insensitive human prostatic cancer cell line (PC‐3) is sensitive to estrogens or progestogens and to elucidate possible mechanisms of action. Both estrogens and progestogens in high doses (10−5 M) suppressed tumor cell growth. At these high doses medroxyprogesterone acetate (MPA) most effectively reduced the uptake of 86rubidium chloride, indicating the strongest effect on ion transport and membrane permeability. Effects on rubidium transport were also seen after estrogen treatment. It is suggested that estrogens and progestogens have direct cytotoxic effects on prostatic carcinoma cells in vitro, possibly by an effect on the cell membrane.
A clinical and immunohistochemical study of papillary adenocarcinoma of the prostate
Authors: Ito Takaaki , Furusato Masakuni , Akiyama Akihito , Kato Hiroyuki , Aizawa Shigeo 
Published: February 2007

AbstractClinical and immunohistochemical studies were conducted to evaluate prostatic papillary adenocarcinoma and prostatic papillary hyperplasia. Subjects consisted of 5 cases of papillary adenocarcinoma and 2 cases of papillary hyperplasia. There is no conclusive clinical factor for preoperative diagnosis, but we attach importance to endoscopic findings. PSA, PAP, high molecular weight cytokeratin, and PCNA were evaluated immunohistochemically. PSA became positive in every instance but one—a case of papillary adenocarcinoma which became ±. PAP was + in all cases, except for 1 case of papillary adenocarcinoma. Basal cells were positive for high molecular weight cytokeratin in 2 cases of papillary hyperplasia but were missing in papillary adenocarcinoma. Although PCNA was free from positive nuclei in papillary hyperplasia, positive nuclei were found in all cases of papillary adenocarcinoma. Considering these immunohistochemical results, papillary adenocarcinoma can be said to originate in the glandular epithelium of the prostate, as does ordinary prostatic carcinoma.
Transurethral microwave thermal therapy: Pathologic findings in the canine prostate
Authors: Bostwick David G. , Larson Thayne R. 
Published: February 2007

AbstractMicrowave irradiation administered by transurethral transducer to the prostate permits focused hyperthermia with resultant tissue ablation; a cooling system within the catheter allows urethral preservation. We evaluated the effect of microwave hyperthermia in 13 dogs receiving 48–79 min of focused irradiation (16–45 watts, intraprostatic temperature >45°C) delivered by a specially‐designed transducer with an operator‐controlled directional antenna (T3, Urologix Inc., Minneapolis, MN); one other dog had transducer placement without irradiation (sham control). After treatment, the dogs were in good health, voiding well without complications, and were sacrificed after 5–38 days. The prostate and vasa deferentia were removed, fixed in 10% formalin, grossly inspected, cut at 5 mm intervals, and serially sectioned with whole mount sections; representative sections of the adjacent rectum and distal bladder were also obtained. All cases were histologically evaluated with prostatic mapping without knowledge of treatment or time of sacrifice. In the acute phase (5–13 days), the prostate showed sharply circumscribed periurethral coagulative necrosis with hemorrhage; necrosis was also seen in the mucosa and bladder wall of those with transducers placed at the bladder neck. In the subacute phase (17 days), the hemorrhagic necrosis was resolving, often with cystically dilated urethra due to sloughed necrotic tissue; the urothelium was intact. By 24–38 days, the necrosis was in the late stages of resolution, with residual patchy acute and chronic inflammation at the periphery, and frequent persistence of megalourethra. In all cases, the prostatic capsule was intact, the urethral mucosa was preserved, and the vasa deferentia and rectum were normal except for two cases with mild fat necrosis. Microwave irradiation allows precisely localized thermal ablation of prostatic tissue and enlargement of the urethral bore without clinical complications in dogs, offering promise as a therapeutic alternative to surgery in select patients with symptomatic prostatic nodular hyperplasia.
Prolactin specifically increases pyruvate dehydrogenase Elα in rat lateral prostate epithelial cells
Authors: Costello L. C. , Liu Y. , Franklin R. B. 
Published: February 2007

AbstractProlactin is an important regulator of prostate citrate production. In rats this regulatory effect of prolactin is specific for lateral prostate, and has no effect on either ventral or dorsal prostate. The mechanisms by which prolactin regulates prostate citrate production have not been elucidated. Two key regulatory enzymes involved in citrate synthesis by prostate epithelial cells are mitochondrial aspartate aminotransferase (mAAT) which provides oxalacetate, and PDH E1α (pyruvate dehydrogenase) which provides acetyl CoA for citrate synthesis. Our previous studies demonstrated that prolactin regulates mAAT. However, an increase in citrate synthesis would require an increase in both oxalacetate and acetyl CoA. Therefore, we investigated the possibility that prolactin might also regulate PDH E1α in LP epithelial cells. The present studies demonstrate that prolactin administration (1 mg/rat) to rats resulted in an increased level of E1α in LP epithelial cells within 6 hr, but had no effect on the E1α level of VP epithelial cells. In vitro studies demonstrated that exposure of freshly prepared LP epithelial cells to prolactin (0.1–1.0 μg/ml) resulted in increased levels of E1α. Prolactin had no effect on either VP or DP epithelial cells. The stimulatory effect of prolactin on E1α was inhibited by actinomycin and cycloheximide, thereby indicating that prolactin stimulated the biosynthesis of E1α. The studies reveal that prolactin specifically stimulates E1α levels of LP epithelial cells, whereas testosterone specifically stimulates E1α levels of VP epithelial cells. At this time, we propose that the effects of prolactin and testosterone involve increased expression of the E1α gene of LP and VP epithelial cells, respectively.
Growth inhibition of androgen‐insensitive human prostate carcinoma cells by a 19‐norsteroid derivative agent, mifepristone
Authors: Lin Ming‐Fong , Kawachi Mark H. , Lin Fen‐Fen , Stallcup Michael R. , Grunberg Steven M. 
Published: February 2007

AbstractMifepristone, also known as RU 486, is a 19‐norsteroid derivative. Currently, mifepristone is being tested in clinical trials on meningioma and breast cancer. In this study we analyzed whether mifepristone could inhibit the growth of human prostate cancer cells including androgen‐insensitive (PC‐3 and DU145) and androgen‐sensitive (LNCaP) cell lines. At 1‐nM concentration, mifepristone exhibited a marginal stimulatory action on LNCaP and PC‐3 cells. Nevertheless, a dose‐dependent growth inhibition on those same cell lines was observed at concentrations of 1 μM and 10 μM. Twenty‐day exposure to the clinically achievable concentration of 1 μM mifepristone resulted in consistent inhibition of all three cell lines studied. Furthermore, this in vitro growth inhibition was reflected in an in vivo nude mouse system. Mifepristone at the dosage of 4 mg/100 g body weight completely suppressed the growth of PC‐3 tumors for 21 days, although this was followed by a growth rate similar to that of the control tumor. To understand the possible mechanism of mifepristone inhibition, PC‐3 cells were exposed to mifepristone in comparison with dexamethasone (Dex), progesterone, and 5 alpha‐dihydrotestosterone (DHT), each at 1‐μM concentration. The results demonstrated that while both DHT and Dex alone had essentially no effect on cell growth, progesterone alone resulted in a 20% growth inhibition, while mifepristone had more than 60% inhibition with a 16‐day exposure. At an equal concentration, the degree of growth inhibition of PC‐3 cells by mifepristone or progesterone was partially diminished by simultaneous exposure to Dex. In conclusion, our results demonstrated that the growth of androgen‐insensitive prostate cancer cells can be directly inhibited by mifepristone in cultures. This in vitro inhibition is reflected in xenografted tumors.
Expression of cellular adhesion molecules on human prostate tumor cell lines
Authors: Rokhlin Oskar W. , Cohen Michael B. 
Published: February 2007

AbstractBy flow cytometric analysis we have examined the expression of cellular adhesion molecules (CAMs) on the surface of four different human prostate tumor cell lines: DU 145, from a brain metastasis; PC 3, from a bone metastasis; LNCaP.FGC, from a lymph node metastasis; and a primary tumor cell line, ND 1. The corresponding ligands for the expressed CAMs were, by and large, extracellular matrix proteins. We detected high‐level expression of ICAM‐1 on three of the four prostate cell lines, whereas LNCaP cells were negative. We observed unstable, heterogeneous expression of E‐cadherin in the cell lines DU 145, PC 3, and ND 1. Flow cytometric cell sorting enabled us to divide PC 3 cells into negative and bright positive subpopulations but, after several cell divisions in culture, sorted cells returned to the original heterogeneous phenotype. The laminin‐specific α6β4 integrin was not expressed by LNCaP, and was expressed at a low level and heterogeneously on DU 145 and PC 3 cell lines. In contrast, ND 1 cells, derived from a primary tumor, showed homogeneous and high‐level expression of the α6β4 integrin. All of the prostate cell lines expressed the RGD‐dependent binding of α3β1 and α5β1 integrins and did not reveal non‐RGD‐dependent α4β1 integrin expression. This finding provides a stimulus to investigate the inhibition capacity of RGD‐containing peptides on the metastatic behavior of prostate tumor cells.
Spontaneous metastasis of PC‐3 cells in athymic mice after implantation in orthotopic or ectopic microenvironments
Authors: Waters David J. , Janovitz Evan B. , Chan Thomas C. K. 
Published: February 2007

AbstractThe ability of subcutaneous, prostatic, and nonprostatic intraabdominal organ microenvironments to influence local tumor growth and metastasis of PC‐3 human prostate carcinoma cells in athymic mice was determined. Tumorigenesis and metastasis of PC‐3 were evaluated 60 days after subcutaneous and intraprostatic (orthotopic) implantation of 5 × 105 PC‐3 cells in 6‐week‐old, male athymic mice. Intraprostatic implantation of PC‐3 cells resulted in paraaortic lymph node metastases in 10 of 10 (100%) mice with prostatic tumors, whereas metastases were present in only 2 of 9 (22%) mice after subcutaneous implantation. Next, we determined whether the urinary bladder (nonprostatic, urogenital microenvironment) or stomach (nonurogenital, intraabdominal microenvironment) would facilitate the metastasis of PC‐3 cells in athymic mice. Tumorigenesis and metastasis were 100% after subserosal implantation of PC‐3 cells within the wall of the urinary bladder (n = 6 mice). Subserosal implantation of PC‐3 cells into the stomach wall (n = 7 mice) also resulted in tumor formation and metastasis to regional lymph nodes in 100% of mice. In all experiments, regional lymph nodes were the most frequent site of metastasis, regardless of implantation site. We conclude that tumor microenvironment factors responsible for the metastasis of PC‐3 cells in athymic mice may not be organ‐specific, since nonprostatic visceral microenvironments are sufficient for predictable metastasis. Use of these models may further our understanding of how tumor microenvironment modulates expression of the metastatic phenotype by human prostate carcinoma cells.