OBJECTIVETo detect HER-2/neu expression in prostate cancer tissues of both androgen dependent and independent groups and to evaluate the role of HER-2/neu in androgen independent prostate cancer.

METHODSImmunohistochemical assay was used in the detection of HER-2/neu in the prostate cancer samples from 30 cases of androgen dependent cancer and 24 cases of androgen independent cancer. The correlation was analyzed between HER-2/neu over-expression and the tumor's clinical stage and Gleason score.

RESULTSThe rates of HER-2/neu over-expression were 10% and 33% in the androgen dependent group and the androgen independent group, significantly higher in the Gleason score >7 group and the clinical stage > T2 group than in the -7 group and the > T2 group (14.29% vs. 26.92%, 34.62% vs. 7.14%, P < 0.01).

CONCLUSIONThe rate of HER-2/neu over-expression is high in androgen independent prostate cancer and is correlated with the tumor stage and Gleason score.

Androgens ; physiology ; Humans ; Immunohistochemistry ; Male ; Neoplasm Staging ; Neoplasms, Hormone-Dependent ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; Receptor, ErbB-2 ; biosynthesis

BACKGROUND: Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis. METHODS: We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results. RESULTS: We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P  = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P  = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P  = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P  = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P  = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P  = 0.002). The statistical powers of positive MR results were all >0.9. CONCLUSION This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.
Female ; Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Neoplasms, Hormone-Dependent ; Reproducibility of Results ; Endometrial Neoplasms ; Lupus Erythematosus, Systemic/genetics* ; Carcinoma, Endometrioid ; Breast Neoplasms ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism.

METHODSLNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy.

RESULTSPSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation.

CONCLUSIONElevated AR transcriptional activity and enhanced expression of PSA induced by PKD3 in response to DHT treatment suggest that PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells.

Cell Line, Tumor ; Humans ; Male ; Neoplasms, Hormone-Dependent ; metabolism ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; Protein Kinase C ; metabolism ; Transcriptional Activation ; Up-Regulation

ObjectiveTo explore the expression of pituitary tumor transforming gene 1 (PTTG1) during the transformation of prostate cancer from androgen-dependent (ADPC) to androgen-independent (AIPC).

METHODSWe established an AIPC cell model LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone-deprived medium for over 3 months. The cell model was verified and the PTTG1 expression in the LNCaP cells was detected by Western blot and RT-PCR during hormone deprivation.

RESULTSThe AIPC cell model LNCaP-AI was successfully established. The PTTG1 expression was gradually increased in the LNCaP cells with the prolonged time of hormone deprivation and the expressions of matrix metalloproteinases MMP-2 and -9 were elevated at the same time.

CONCLUSIONSThe expression of PTTG1 is increased gradually in AIPC, which may be a target of gene therapy for advanced prostate cancer.

Blotting, Western ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasms, Hormone-Dependent ; Prostatic Neoplasms ; enzymology ; genetics ; Securin ; genetics

OBJECTIVETo construct a eukaryotic expression vector carrying human VEGF RNAi and to study the effect of RNA interference on VEGF expression in prostate carcinoma.

METHODSVEGF RNAi was synthesized, inserted into the RNA interference eukaryotic expression vector, and confirmed by the result sequencing. The vector was transfected into prostate cancer PC-3, the VEGF expression detected by Western blot and the cell inhibiting rate determined by MTT.

RESULTSThe VEGF RNAi eukaryotic expression vector was successfully constructed. Compared with the empty vector group and the control group, the amount of VEGF protein expression was obviously decreased in the VEGF RNAi group. The inhibiting rates were 23.5% , 33. 5% and 40. 8% at 24, 48 and 72 h respectively.

CONCLUSIONVEGF RNAi can inhibit the protein expression and growth of PC-3, which provides an experimental base for the biological therapy of prostate cancer.

Cell Line, Tumor ; Gene Expression ; Humans ; Male ; Neoplasms, Hormone-Dependent ; genetics ; metabolism ; Prostatic Neoplasms ; genetics ; metabolism ; RNA Interference ; Transfection ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

OBJECTIVETo study the paracrine effect of the neuroendocrine differentiation cells and its influence on androgen receptor expression of prostate carcinoma cells.

METHODSEstablished an in vitro induced model of neuroendocrine differentiation of prostate carcinoma (LNCaP(NE), PC-3M(NE)), and investigate the proliferation effect of neuroendocrine phenotype cells (LNCaP(NE), PC-3M(NE)) on other non-neuroendocrine phenotype cells (LNCaP, PC-3M) by feeding non-neuroendocrine phenotype cells with the medium pre-incubated with induced neuroendocrine phenotype cells. It was also tested the regulation of androgen receptor mRNA and androgen receptor protein expression of LNCaP(NE) cells on LNCaP cells by reverse transcriptase polymerase chain reaction and Western Blot in the presence or absence of androgens.

RESULTSThe medium pre-incubated with PC-3M(NE) cells could promote the proliferation of PC-3M cells. The medium pre-incubated with LNCaP(NE) cells could promote the proliferation of LNCaP cells, and reduce the expression of androgen receptor in the latter in the absence of androgens, but the negative results were observed in the presence of androgens.

CONCLUSIONSThe neuroendocrine phenotype cells of prostate cancer can reduce the expression of androgen receptor in prostate cancer cells and promote them to proliferate by means of paracrine in the blockade of androgens.

Androgens ; pharmacology ; Cell Division ; drug effects ; Cell Line, Tumor ; Humans ; Male ; Neoplasms, Hormone-Dependent ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; Receptors, Androgen ; metabolism

BACKGROUND: Human pituitary adenoma (PA) is a common intracranial tumor, but the mechanism underlying tumorigenesis has not been established. Functional inactivation of retinoblastoma protein (pRb) following cyclin D1- and cyclin-dependent kinase (CDK) 4-dependent hyperphosphorylation is one of the most important mechanisms in tumor cell proliferation. We evaluated immunohistochemical expressions of cyclin D1, CDK4 and phosphorylated pRb (p-pRb) in 50 PAs to investigate a role for functional inactivation of pRb associated with cyclin D1/CDK4 overexpression in pituitary tumorigenesis and to correlate it with clinicopathologic variables. METHODS: Fifty human PAs were immunohistochemically stained for cyclin D1, CDK4 and p-pRb (Thr 356). Correlations between their expression and the clinicopathologic characteristics were statistically analyzed. RESULTS: Cyclin D1 and CDK4 were overexpressed in 56% and 64%, respectively; pRb was hyperphosphorylated in 64%. Forty one cases (82%) showed one or more of these altered expressions. Overexpressions of cyclin D1 and CDK4 were correlated with functional pRb inactivation. Cyclin D1 overexpression was associated with apoplexy and growth hormone production. CONCLUSIONS: Functional inactivation of pRb associated with the cyclin D1/CDK4 overexpression might play a key role in human pituitary tumorigenesis. CDK4 worked in concert with cyclin D1 to hyperphosphorylate pRb. Pituitary apoplexy appeared to be associated with cyclin D1 overexpression.
Cell Proliferation ; Cell Transformation, Neoplastic ; Cyclin D1 ; Cyclin-Dependent Kinase 4 ; Cyclins ; Growth Hormone ; Humans ; Immunohistochemistry ; Phosphotransferases ; Pituitary Apoplexy ; Pituitary Neoplasms ; Retinoblastoma Protein ; Stroke

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil(R)) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.
Cancer Vaccines/*immunology ; Cell Line, Tumor ; Dendritic Cells/cytology/drug effects/*immunology ; Dinoprostone/*pharmacology ; Humans ; Immunologic Factors/*pharmacology ; Interferon-alpha/*pharmacology ; Lipopolysaccharides/toxicity ; Male ; Neoplasms, Hormone-Dependent/*immunology ; Phenotype ; Picibanil/*pharmacology ; Prostatic Neoplasms/*immunology ; T-Lymphocytes, Cytotoxic/immunology

OBJECTIVETo investigate the effect of dihydrotestosterone (DHT) on the gene transcriptions and expressions of Smad3 and Smad4 in androgen dependent prostate cancer cell line LNCaP, and whether this effect can be suppressed by the androgen receptor inhibitor flutamide.

METHODSThe androgen dependent prostate cancer cell line LNCaP was cultured in RPMI 1640 medium and treated with different concentrations of DHT(2, 10, 50 nmol/L) and flutamide (100 nmol/L). Quantitative reverse transcription PCR (RT-PCR) was used to detect the mRNAs of Smad3 and Smad4. The expressions of Smad3 and Smad4 protein were detected by Western blot assay.

RESULTSCompared with the control group without any DHT or flutamide, higher concentration(10, 50 nmol/L) of DHT enhanced the transcription of Smad3 mRNA (P <0.05). Serial concentrations of DHT increased the expression of Smad3 protein(P < 0.05). Flutamide inhibited the up-regulation of both Smad3 mRNA transcription and expression significantly (P <0.05). 10 nmol/L DHT significantly suppressed the transcription of Smad4 (P <0.05). There was considerable suppressions of Smad4 expression at the presence of DHT in different concentrations (P < 0.05). And the degree of this suppression was more significant than that of DHT on Smad4 mRNA transcription. Flutamide inhibited the suppressive effects of DHT on both Smad4 mRNA transcription and expression.

CONCLUSIONDHT can enhance the transcription and expression of Smad3, while it decreases the transcription and expression of Smad4 in LNCaP cell line. There is a possible crosstalk between the AR signal and TGF-beta signal passways at the level of Smads.

Androgens ; physiology ; Cell Line, Tumor ; Dihydrotestosterone ; pharmacology ; Flutamide ; pharmacology ; Humans ; Male ; Neoplasms, Hormone-Dependent ; metabolism ; Prostatic Neoplasms ; metabolism ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Smad3 Protein ; biosynthesis ; genetics ; Smad4 Protein ; biosynthesis ; genetics ; Transcription, Genetic

OBJECTIVETo explore the apoptosis induction by curcumin in androgen-dependent prostate cancer cell line LNCaP).

METHODSAfter LNCaP cells were induced by 10, 25, 50, 75, 100 micromol/L curcumin respectively, the cell activity was assayed by MTT at 5, 12 and 24 hours. Flow cytometry and electronic microscopy were adopted to observe cell cycle and morphological changes of LNCaP cells at 24 hours. After 5 hours, the expression of IkappaBalpha in LNCaP cells was detected by Western blotting.

RESULTSThe growth of LNCaP cells was suppressed obviously by curcumin in dose-dependent and time-dependent manners in vitro. There were significant differences in inhibition rate among different concentrations and time groups (P < 0.05). Furthermore, curcumin could arrest the cell cycle of LNCaP cells at G2/M phase in a dose-dependent manner (P <0.01). The ratios of apoptosis were significantly higher than those of controls (P < 0. 5). Curcumin could lead to characteristic morphological changes of apoptosis in LNCaP cells after 24 hours. The expression of IkappaBalpha in LNCaP cell did not show marked changes after the exposure to different concentrations of curcumin within 5 hours.

CONCLUSIONCurcumin can suppress the growth of LNCaP, and promotes their apoptosis.

Apoptosis ; drug effects ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Curcumin ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; I-kappa B Proteins ; biosynthesis ; Male ; NF-KappaB Inhibitor alpha ; Neoplasms, Hormone-Dependent ; Prostatic Neoplasms ; metabolism ; pathology