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The radiation response of androgen-refractory prostate cancer cell line C4-2 derived from androgen-sensitive cell line LNCaP.

ABSTRACT: Radiation therapy is a relatively effective therapeutic method for localized prostate cancer (PCa) patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therapeutic synergy between radiotherapy and androgen ablation treatment provides a promising strategy for improving the clinical outcome. Accordingly, the androgen deprivation-induced signaling pathway may also mediate radiosensitivity in PCa cells. The C4-2 cell line was derived from the androgen-sensitive LNCaP parent line under androgen-depleted condition and had acquired androgen-refractory characteristics. In our study, the response to radiation was evaluated in both LNCaP and C4-2. Results showed that C4-2 cells were more likely to survive from irradiation and appeared more aggressive in their resistance to radiation treatment compared with LNCaP, as measured by clonogenic assays and cell viability and cell cycle analyses. Gene expression analyses revealed that a set of genes involved in cell cycle arrest and DNA repair were differentially regulated in LNCaP and C4-2 in response to radiation, which was also consistent with the radiation-resistant property observed in C4-2 cells. These results strongly suggested that the radiation-resistant property may develop with progression of PCa to androgen-independent status. Not only can the LNCaP and C4-2 PCa progression model be applied for investigating androgen-refractory progression, but it can also be used to explore the development of radiation resistance in PCa.

SUBMITTER: Xie BX

PROVIDER: S-EPMC3739257 | biostudies-other | 2010 May

REPOSITORIES: biostudies-other

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Lncap-AI prostate cancer cell line establishment by Flutamide and androgen-free environment to promote cell adherent.

Project description:BackgroundTo establish castration-resistant prostate cancer (CRPC) - Lncap androgen-independent (AI) cell line from Lncap androgen-dependent (AD) cell line, and explore the different molecular biological between these two cell lines.MethodsThe Lncap-AD cell line was cultured and passaged 60 times over 16 months. The morphology of the Lncap-AI cell line was observed. AR levels identification were detected in qRT-PCR and Western Blot assay. CCK-8, EdU assay, wound healing assay and cell adhesion assays were used to observe the ability of proliferation, migration, and adhesion. SEM and TEM were used to observe microculture structure. At last, the PSA secrete ability was evaluated by Elisa assay.ResultsThe Lncap-AD cell line was cultured and passaged 60 times over 16 months. The Lncap-AI cell line showed a morphologic change at the end stage of culture, the cells turned slender and cell space turned separated compared to the Lncap-AD cell line. The relative levels of AR-related genes in the Lncap-AI cell line were up-regulation compared to the Lncap-AD cell line both in mRNA and protein levels. The expression of AR and HK2 proteins were influenced and down-regulation by Enzalutamide in the Lncap-AD cell line, but no obvious difference in Lncap-AI cell lines. Lncap-AI cell line showed strong viability of proliferation, migration, and adhesion by CCK-8, EdU assay, wound healing assay, and adhesion assay. The microstructure of Scanning Electron Microscopy (SEM) showed many synapses in the Lncap-AI cell line and PC3 cell line, but not in the Lncap-AD cell line. At last, the PSA secrete ability was evaluated by Elisa assay, and PCa cell lines showed no significant difference.ConclusionSimulation of CRPC progression, Lncap-AD cell line turned to Lncap-AI cell line with androgen deprivation therapy.

| S-EPMC9706963 | biostudies-literature

Comparison of the prostate cancer cell line LNCaP and its androgen insensitive derivative C4-2B

2007-08-07 | GSE7702 | GEO

Comparison of the prostate cancer cell line LNCaP and its androgen insensitive derivative C4-2B

Project description:LNCaP and its androgen insensitive derivative were profiled in order to identify genes differentially expressed during the conversion to androgen insensitivity. This experiment was performed due to the presence of an ins(7;14) localizing the entire ETV1 locus to chr 14 in LNCaP and C4-2B prostate cancer cells. Keywords: cell type comparison LNCaP and C4-2B were both hybridized to Agilent Whole Human Genome Oligonucleotide Microarrays, with a commercially obtained pool of benign prostate RNA serving as the reference for both cell lines. Dye flips for both cell lines were also performed

2007-08-07 | E-GEOD-7702 | biostudies-arrayexpress

Androgen-sensitive glycomembrane protein expression in LNCaP prostate tumor cells

Project description:Aberrant androgen receptor (AR)-mediated transcription is a critical driver in progression of human prostate cancer. It's known that different doses of androgens can elicit differential transcriptional and proliferative responses in prostate-tumor cells. Here, we set out to examine the androgenic regulation of glycoprotein expression in the membrane fraction of prostate-tumor cells that could serve as mediators or markers of androgen-induced proliferative responses observed in prostate-tumor cells. A bioanalytical workflow involving lectin-affinity chromatography and label-free quantitative mass spectrometry was used to identify androgen-sensitive glycomembrane protein expression associated with androgen-mediated proliferation. This study would facilitate the identification of surface membrane proteins involved in androgen-mediated proliferation and provide potential therapeutic targets in the detection treatment of proliferation prostate-tumors.

2022-03-01 | PXD002913 | Pride

Comparative genomic and transcriptomic analyses of LNCaP and C4-2B prostate cancer cell lines.

Project description:The LNCaP and C4-2B cell lines form an excellent preclinical model to study the development of metastatic castration-resistant prostate cancer, since C4-2B cells were derived from a bone metastasis that grew in nude mice after inoculation with the LNCaP-derived, castration-resistant C4-2 cells. Exome sequencing detected 2188 and 3840 mutations in LNCaP and C4-2B cells, respectively, of which 1784 were found in both cell lines. Surprisingly, the parental LNCaP cells have over 400 mutations that were not found in the C4-2B genome. More than half of the mutations found in the exomes were confirmed by analyzing the RNA-seq data, and we observed that the expressed genes are more prone to mutations than non-expressed genes. The transcriptomes also revealed that 457 genes show increased expression and 246 genes show decreased expression in C4-2B compared to LNCaP cells. By combining the list of C4-2B-specific mutations with the list of differentially expressed genes, we detected important changes in the focal adhesion and ECM-receptor interaction pathways. Integration of these pathways converges on the myosin light chain kinase gene (MLCK) which might contribute to the metastatic potential of C4-2B cells. In conclusion, we provide extensive databases for mutated genes and differentially expressed genes in the LNCaP and C4-2B prostate cancer cell lines. These can be useful for other researchers using these cell models.

| S-EPMC3938550 | biostudies-literature

Characterization of a novel metastatic prostate cancer cell line of LNCaP origin.

Project description:The LNCaP cell line was originally isolated from the lymph node of a patient with metastatic prostate cancer. Many cell lines have been derived from LNCaP by selective pressures to study different aspects of prostate cancer progression. When injected subcutaneously into male athymic nude mice, LNCaP and its derivatives rarely metastasize.Here, we describe the characteristics of a new LNCaP derivative, JHU-LNCaP-SM, which was generated by long term passage in normal cell culture conditions.Short tandem repeat (STR) analysis and genomic sequencing verified JHU-LNCaP-SM derivation from parental LNCaP cells. JHU-LNCaP-SM cells express the same mutated androgen receptor (AR) but unlike LNCaP, are no longer androgen dependent for growth. The cells demonstrate an attenuated androgen responsiveness in transcriptional assays and retain androgen sensitive expression of PSA, AR, and PSMA. Unlike parental LNCaP, JHU-LNCaP-SM cells quickly form subcutaneous tumors in male athymic nude mice, reliably metastasize to the lymph nodes and display a striking intra-tumoral and spreading hemorrhagic phenotype as tumor xenografts.The JHU-LNCaP-SM cell line is a new isolate of LNCaP, which facilitates practical, preclinical studies of spontaneous metastasis of prostate cancer through lymphatic tissues.

| S-EPMC4729204 | biostudies-literature

Diastereomers of the brominated flame retardant 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane induce androgen receptor activation in the hepg2 hepatocellular carcinoma cell line and the lncap prostate cancer cell line.

Project description:BackgroundReported incidences of prostate cancer and masculinization of animals indicate a release of compounds with androgenic properties into the environment. Large numbers of environmental pollutants have been screened to identify such compounds; however, not until recently was 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) identified as the first potent activator of the human androgen receptor (hAR). TBECH has been found in beluga whales and bird eggs and has also been found to be maternally transferred in zebrafish.ObjectivesIn the present study we investigated interaction energies between TBECH diastereomers (alpha, beta, gamma, and delta) and the hAR, and their ability to activate the receptor and induce prostate-specific antigen (PSA) expression in vitro.MethodsWe performed computational modeling to determine interaction energies between the ligand and the AR ligand-binding site, and measured in vitro competitive binding assays for AR by polarization fluorometry analysis. We used enzyme-linked immunosorbent assays to determine PSA activity in LNCaP and HepG2 cells.ResultsWe found the gamma and delta diastereomers to be more potent activators of hAR than the alpha and beta diastereomers, which was confirmed in receptor binding studies. All TBECH diastereomers induced PSA expression in LNCaP cells even though the AR present in these cells is mutated (T877A). Modeling studies of LNCaP AR revealed that TBECH diastereomers bound to the receptor with a closer distance to the key amino acids in the ligand-binding domain, indicating stronger binding to the mutated receptor.ConclusionsThe present study demonstrates the ability of TBECH to activate the hAR, indicating that it is a potential endocrine disruptor.

| S-EPMC2799458 | biostudies-literature

Soluble factors derived from stroma activated androgen receptor phosphorylation in human prostate LNCaP cells: roles of ERK/MAP kinase.

Project description:BackgroundAccumulated evidence suggests stromal-epithelial interactions are critical to the progression of prostate cancer. In this study, we characterized AR phosphorylation in LNCaP cells co-cultured with the conditioned medium (CM) from human prostate stromal fibroblasts.MethodsCM harvested from prostate stromal fibroblasts was added to LNCaP cells, and both anchorage-dependent and -independent growth was determined. Status of AR phosphorylation at Ser-81 and Ser-213 was assessed by immunoblot analysis. ERK kinase activity was measured using MBP-2 protein as the substrate.ResultsThe growth of LNCaP cells on plastic dishes increased by 1.7-fold upon exposure to stromal CM or androgen, and their combination resulted in additive growth (2.4-fold). Anchorage-independent growth of LNCaP cells in soft agar, however, was induced synergistically at 80-fold by both stromal CM and androgen. Stromal CM or androgen alone induced LNCaP cell growth by 10- and 26-fold, respectively. We observed ERK kinase inhibitor, U0126, but not phosphatidylinositol 3-kinase (PI-3K), LY294002, or protein kinase A (PKA) inhibitor, H-89, inhibited stromal CM or androgen-induced PSA promoter luciferase activities, and anchorage-independent growth of LNCaP cells. Our results demonstrated for the first time how stromal CM acts in synergy with androgen by activation of ERK kinase and AR phosphorylation at Ser-81 but not Ser-213, for AR-regulated PSA promoter and anchorage-independent growth of human prostate cancer cells.ConclusionsA stromal factor-activated ERK pathway mediated by AR phosphorylation at Ser-81 could be responsible for stimulating the growth of human prostate cancer cells.

| S-EPMC2753603 | biostudies-literature

Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach.

Project description:BackgroundHigh throughput sequencing-by-synthesis is an emerging technology that allows the rapid production of millions of bases of data. Although the sequence reads are short, they can readily be used for re-sequencing. By re-sequencing the mRNA products of a cell, one may rapidly discover polymorphisms and splice variants particular to that cell.ResultsWe present the utility of massively parallel sequencing by synthesis for profiling the transcriptome of a human prostate cancer cell-line, LNCaP, that has been treated with the synthetic androgen, R1881. Through the generation of approximately 20 megabases (MB) of EST data, we detect transcription from over 10,000 gene loci, 25 previously undescribed alternative splicing events involving known exons, and over 1,500 high quality single nucleotide discrepancies with the reference human sequence. Further, we map nearly 10,000 ESTs to positions on the genome where no transcription is currently predicted to occur. We also characterize various obstacles with using sequencing by synthesis for transcriptome analysis and propose solutions to these problems.ConclusionThe use of high-throughput sequencing-by-synthesis methods for transcript profiling allows the specific and sensitive detection of many of a cell's transcripts, and also allows the discovery of high quality base discrepancies, and alternative splice variants. Thus, this technology may provide an effective means of understanding various disease states, discovering novel targets for disease treatment, and discovery of novel transcripts.

| S-EPMC1592491 | biostudies-literature

Ophiopogonin D' induces RIPK1‑dependent necroptosis in androgen‑dependent LNCaP prostate cancer cells.

Project description:Ophiopogonin D' (OPD') is a natural compound extracted from Ophiopogon japonicus, which is a plant used in traditional Chinese medicine. Our previous study has indicated that OPD' exhibits antitumor activity against androgen‑independent prostate cancer (PCa), but the effects and the underlying molecular mechanism of action of OPD' in androgen‑dependent PCa were unclear. In the present study, OPD' induced significant necroptosis in androgen‑dependent LNCaP cancer cells by activating receptor‑interacting serine/threonine‑protein kinase 1 (RIPK1). Exposure to OPD' also increased Fas ligand (FasL)‑dependent RIPK1 protein expression. The OPD'‑induced necroptosis was inhibited by a RIPK1 inhibitor necrostatin‑1, further supporting a role for RIPK1 in the effects of OPD´. The antitumor effects of OPD' were also inhibited by a mixed lineage kinase domain‑like protein (MLKL) inhibitor necrosulfonamide. Following treatment with inhibitors of RIPK1 and MLKL, the effects of OPD' on LNCaP cells were inhibited in an additive manner. In addition, co‑immunoprecipitation assays demonstrated that OPD' induced RIPK3 upregulation, leading to the assembly of a RIPK3‑MLKL complex, which was independent of RIPK1. Furthermore, OPD' increased the expression of Fas‑associated death domain, which is required to induce necroptosis in LNCaP cells. OPD' also regulated the expression levels of FasL, androgen receptor and prostate‑specific antigen in a RIPK1‑dependent manner. These results suggested that OPD' may exhibit potential as an anti‑PCa agent by inducing RIPK1‑ and MLKL‑dependent necroptosis.

| S-EPMC6959467 | biostudies-literature

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