Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor beta is a strong growth inhibitor for many types of normal and transformed cells, although little is known on the mechanism of this anti-proliferative effect. The human lung adenocarcinoma cell line A549 is growth arrested by TGF-beta 1 and serves as a model for studying this effect. We describe that, concurrent with the inhibition of A549 cell growth, TGF-beta 1 treatment causes a dramatic reduction in the level of expression of the amphiregulin (AR) gene, a recently identified member of the EGF/TGF alpha family. Similar results were also observed with TGF-beta 2. Peak inhibition occurred at 24 hr of treatment and was reversible upon removal of TGF-beta 1. The level of AR protein secreted by A549 cells was also decreased by TGF-beta 1. In contrast, TGF-alpha mRNA was not detected in these cells regardless of TGF-beta 1 treatment. Another TGF-beta inhibited cell line, PC-3 (human prostatic adenocarcinoma) also exhibited a decrease in AR message levels following exposure to TGF-beta 1. The growth inhibitory effects of TGF-beta may in part be mediated by modulation of AR expression.
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PMID:Regulation of amphiregulin mRNA by TGF-beta in the human lung adenocarcinoma cell line A549. 145 26

We have obtained a cDNA clone coding for human transforming growth factor (TGF)-beta 2. The clone was isolated from a tamoxifen-treated human prostatic adenocarcinoma cell line (PC-3) using oligonucleotide probes based on the partial amino acid sequence of purified TGF-beta 2. The cDNA sequence predicts that TGF-beta 2 is synthesized as a 442-amino-acid polypeptide precursor from which the mature 112-amino-acid TGF-beta 2 subunit is derived by proteolytic cleavage. The proteins coded for by the human TGF-beta 1 and TGF-beta 2 cDNAs show an overall homology of 41%. The mature and amino-terminal precursor regions show 71% and 31% homology, respectively. Northern blot analysis identified TGF-beta 2 transcripts of 4.1, 5.1, and 6.5 kb using mRNA from several different sources. Analysis of polyadenylated RNA from tamoxifen-treated PC-3 cells showed that these cells contain higher numbers of transcripts for TGF-beta 1 than for TGF-beta 2, although they produce more TGF-beta 2 protein than TGF-beta 1. This suggests that there is a post-transcriptional level of regulation for the production of these proteins.
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PMID:Transforming growth factor-beta 2: cDNA cloning and sequence analysis. 316 14

Human type beta 2 transforming growth factor (hTGF-beta 2) was purified from tamoxifen-supplemented, serum-free medium conditioned by the human prostatic adenocarcinoma cell line PC-3. The purification of hTGF-beta 2 was monitored in a growth inhibition assay and was achieved by batch purification on methylsilyl-controlled pore glass, followed by gel permeation chromatography and reversed-phase high-performance liquid chromatography. The overall recovery of hTGF-beta 2 was 75% of the initial activity and yielded 22 micrograms of hTGF-beta 2/L of conditioned medium. The concentration of hTGF-beta 2 required for half-maximal inhibition of Mv 1 Lu mink lung epithelial cells (CCl-64) was approximately 5 pM when assayed in the presence of 10% fetal bovine serum. The purified hTGF-beta 2 has a molecular weight of 24,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and consists of two disulfide-linked, apparently identical polypeptide chains, with a molecular weight of 13,000. The amino-terminal sequence of hTGF-beta 2 was determined. Alignment of the amino acid sequences of hTGF-beta 2 and hTGF-beta reveals statistically significant sequence homology. On the basis of the extensive amino acid sequence homology, we propose the term TGF-beta 2 for this newly isolated polypeptide. The reported results suggest that TGF-beta (TGF-beta 1) and TGF-beta 2 may have evolved from a common progenitor.
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PMID:Human transforming growth factor type beta 2: production by a prostatic adenocarcinoma cell line, purification, and initial characterization. 347 30

Rats transplanted with the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma were castrated and treated with either estrogen or vehicle alone for short periods (4 hr, 12 hr, 24 hr) and for 6 weeks. In these tumors the expression of TGF-beta 1, TGF-beta type-I and type-II receptors (TGF-beta RI, TGF-beta RII) was examined by immunohistochemistry. Apoptotic cells were identified by in situ nick and labelling (TUNEL). Tumor growth was retarded by castration and even more by additive estrogen treatment. The epithelium of the untreated tumors stained weakly for TGF-beta 1 and TGF-beta RI, but TGF-beta RII was not detected. Castration induced moderate TGF-beta 1 immunoreactivity in a major part of the glandular epithelium after 24 hr. After 12 hr already, castration plus estrogen resulted in an intense staining for TGF-beta 1 in the basal epithelial cells, some of which also showed an apoptotic appearance. The percentage of cells having stained positive for TGF-beta 1 was significantly higher in the estrogen-treated groups than in the castrated group after 12 hr, and its elevated TGF-beta 1 level remained at 6 weeks. Notably, the increased immunoexpression of TGF-beta 1 occurred before the onset of induction of apoptosis. In parallel with the upregulation of TGF-beta 1 after castration, the expression of its receptors. TGF-beta RI and RII, was induced and was further enhanced by the additive estrogen treatment. The number of intensely stained TGF-beta 1 tumor cells showed a strong correlation with the number of apoptotic tumor cells identified by TUNEL in the whole material. Furthermore, TGF-beta 1 immunoreactivity co-localized with the presence of apoptotic cells in the estrogen-treated tumors at 6 weeks after castration.
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PMID:Estrogen induces apoptosis in a rat prostatic adenocarcinoma: association with an increased expression of TGF-beta 1 and its type-I and type-II receptors. 875 18

In previous studies we demonstrated that the growth of human prostatic adenocarcinoma is associated with aberrant accumulation of transforming growth factor (TGF) beta1, a growth factor that has been shown to be a potent inhibitor of epithelial cell proliferation. We investigated the expression of TGF-beta receptor II (TGFbetaR-II) in benign prostate tissue and in prostate cancer using standard immunohistochemical techniques. Quantitation of immunopositivity for TGFbetaR-II was assessed on a visual analogue scale ranging from 0 (absence of staining) to 4+ (intensely positive staining). All of the benign glandular epithelia stained intensely, either 3+ or 4+, representative of the ubiquitous nature of TGFbetaR-II in normal tissue. Overall, staining was reduced in prostate cancer sections, and there was progressively diminished staining as the histological grade of the cancer increased (P < 0.01, Kruskal-Wallis test). This immunohistochemical study indicates that a decline in the levels of TGFbetaR-II is correlated with advancing histological aggressiveness of the cancer and suggests that aberrant TGFbetaR-II function may play a role in human prostate carcinogenesis.
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PMID:Reduced levels of transforming growth factor beta receptor type II in human prostate cancer: an immunohistochemical study. 981 13

An immunohistochemical and semiquantitative comparative study of transforming growth factor beta 1 (TGF-beta 1) and its receptor types I (TGF-beta RI) and II (TGF-beta RII) was carried out in normal prostates and in the prostates from men with benign prostatic hyperplasia (BPH), and men with prostatic adenocarcinoma. Immunoreaction to TGF-beta 1 was limited to the basal epithelial cells in the normal prostates. Some cells in the connective tissue stroma were also stained. In BPH immunolabelling was also observed in columnar (secretory) cells of the epithelium. In prostatic adenocarcinoma, all epithelial cell types were intensely immunostained. Some stromal cells were also stained. Immunostaining to TGF-beta RI was only present in the basal cells in normal prostates. In BPH, this immunoreaction was found in the whole epithelium and in some stromal cells. In prostatic cancer, the immunostaining pattern for this receptor was similar to that of BPH but more intense in the epithelial cells. Immunoreactivity to TGF-beta RII appeared in some basal cells and some scattered columnar cells of the normal prostate epithelium. In the BPH sections, this pattern was maintained, and a weak immunolabelling was also observed in the stroma. In prostate cancer, all epithelial cells appeared intensely labelled. In the stroma, immunolabelling was similar to that of the BPH specimens. The results of the present study suggest that, in normal prostates, only the basal cells of the epithelium possess both receptor types, and hence can transduce TGF-beta 1 signal intracellularly. The basal cells can also secrete this growth factor which would act as an autocrine inhibitory growth factor for them. In addition, TGF-beta 1 is secreted in some zones by stromal cells, acting then as a paracrine growth factor for basal cells in those areas. In BPH, in addition to the basal cells, some secretory columnar cells also secrete TGF-beta 1 and possess both types of TGF-beta 1 receptors, and thus, both epithelial cell types are susceptible to TGF-beta 1 action. Since both receptor types are also present in some stromal cells, these cells also perform an autocrine secretion, in addition to their paracrine secretion to the epithelial cells. TGF-beta RIIs seem to be more numerous than TGF-beta RIs and this lead us to hypothesize that these incomplete receptors might be a protection against the inhibition caused by TGF-beta 1 action. In prostatic carcinoma all cell types display the same characteristics as in BPH, although both receptor types are found in similar numbers, and thus, the above mentioned protection would not occur.
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PMID:Transforming growth factor beta 1 and its receptor types I and II. Comparison in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma. 993 28

Transforming growth factor-beta1 (TGF-beta1) inhibits epithelial cell proliferation in the normal prostate. Prostate tumours express high levels of TGF-beta1, and seem to acquire resistance to its anti-proliferative effects with tumour progression. In this study, TGFbeta variations with tumour progression were examined in the Dunning prostatic adenocarcinoma model. Expression of TGF-beta1 and TGFbeta receptor type I and type II (TGFbeta-RI and TGFbeta-RII) in rat dorsolateral prostate (DLP) and Dunning tumour sublines (PAP, AT-1, AT-2, AT-3 and MatLyLu) was examined in vitro and in vivo, using competitive reverse transcription-polymerase chain reaction (RT-PCR), Northern and Western blot, and immunohistochemistry. All tumours expressed elevated levels of TGF-beta1 and TGFbeta-RI mRNA, when compared with the DLP (P < or = 0.05). All tumours except MatLyLu also expressed elevated levels of TGFbeta-RII mRNA (P < or = 0.05). Interestingly, TGFbeta-RII protein levels were very low in the highly metastatic AT-3 and MatLyLu tumours in vivo, when compared with levels in the PAP, AT-1, and AT-2 tumours. This difference was not detected for the AT-1, AT-2, and AT-3 cells in vitro. Immunostaining of TGF-beta1, TGFbeta-RI, and TGFbeta-RII was localised principally in normal and tumour epithelial cells, and occasionally in smooth muscle cells. In conclusion, high expression of TGF-beta1 and TGFbeta-RI and low expression of TGFbeta-RII may contribute to tumour progression and metastasis in the Dunning prostatic adenocarcinoma model.
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PMID:Alterations of transforming growth factor beta1 (TGF-beta1) and TGFbeta receptor expressions with progression in Dunning rat prostatic adenocarcinoma sublines. 1042 20

As a result of the association between ionizing irradiation and the induction of inflammatory and fibrogenic cytokines, circulating levels of IL-1alpha, macrophage colony stimulating factor (M-CSF) and TGFbeta were measured in a group of 37 patients who presented with well-defined adenocarcinoma of the prostate and were treated with wide-field pelvic (WFP) + prostate boost (PB) radiotherapy (xRT) according to RTOG protocols 94-08 and 94-13. First and foremost, patients with prostate cancer (PC) were found to have a significantly (p<0.05) elevated plasma level of the three cytokines prior to treatment. Moreover, during WFP + PB xRT, these circulating cytokine levels were further elevated, the elevation occurring in the form of cyclic waves; the concurrent waves of elevated IL-1alpha and M-CSF preceding that of TGFbeta. In addition to providing support for the existence of a humoral response to xRT in patients receiving WFP + PB xRT, the data demonstrated a significant correlation between the integral radiation dose (ID) and the temporal expression and magnitude of plasma IL-1alpha, M-CSF and TGFbeta levels in patients that had received 1-5 fractions (1.8-9Gy) of WFP + PB xRT. Thereafter, the appearance of elevated waves of cytokine expression in the patient's plasma continued independent of additional fractions of WFP + PB xRT.
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PMID:Cytokine profiles in patients receiving wide-field + prostate boost radiotherapy (xRT) for adenocarcinoma of the prostate. 1296 40

TGF-beta activated kinase (TAK1) plays a critical role in the TGF-beta signaling transduction pathway. By screening a human 18-week fetal brain library, we isolated a novel human TAK1-like (TAKL) gene. The gene encoded a putative protein of 242 amino acids, which shared a homology with human, mouse, and Xenopus TAK1. The TAKL gene was located in chromosome 21q21. Northern blot analysis revealed that the TAKL mRNA was expressed predominantly in peripheral blood leukocytes and ubiquitously in human adult and fetal tissues. TAKL was also expressed strongly in breast carcinoma GI-101, colon adenocarcinoma GI-112, and prostatic adenocarcinoma PC3.
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PMID:Cloning and characterization of a novel human TGF-beta activated kinase-like gene. 1516 26

Immunohistochemical study of histological sections and immunochemical study in supernatants of primary cultures demonstrated a marked increase of the factor production in the regions of the background changes outside foci of carcinoma invasive growth. There was no difference in the type of expression of TGFbeta-I and TGFbeta-II receptors in morphologically different regions of the tumour. TGFbeta-I is considered as a principal factor that mediates hyperplastic reaction of the stroma in prostatic adenocarcinoma outside the zones of invasive growth. Formation of reactive stroma, in the authors' opinion, plays the role of a defensive mechanism hindering invasion of tumour cells into the connective tissue and its progression.
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PMID:[Role of a transforming growth factor beta-1 in regulation of invasive growth of prostatic adenocarcinoma]. 1531 53


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