scholarly journals Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hox Genes ◽  
Human Cancer ◽  
Specific Expression ◽  
Hox Gene ◽  
Human Cancer Cell Lines ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Hox Code ◽  
Specific Expression Pattern

AbstractHOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.

scholarly journals Loss of HOXB13 expression in neuroendocrine prostate cancer

2020 ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immunohistochemical Staining ◽  
Prostate Adenocarcinoma ◽  
Tissue Type ◽  
Clear Cut ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Rnaseq Data ◽  
Hox Code

AbstractHOXB13, the most posterior HOX B gene, is primarily expressed in the prostate. Using immunohistochemical staining, we evaluated the expression of HOXB13 in prostatic tissues. We found that HOXB13 was expressed in both benign prostatic tissues and prostate adenocarcinoma (AdPCa) but its expression was reduced or lost in neuroendocrine prostate cancer (NEPCa). Additionally, using RNAseq data of HOXs in cell lines derived from various tissue origins, we established HOX codes for these tissue types. We applied the HOX codes to PCa samples and found that the majority of AdPCa samples sustained the prostate-specific HOX code but the majority of NEPCa samples lost it. Our analysis also showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue type. This indicates that NEPCa tumors lose prostate identity but do not gain a clear-cut new tissue identity. Finally, we treated PCa cells with all trans retinoic acid and found that the reduced/lost HOXB13 expression can be reverted, as can AR and AR targets. Taken together, our data indicate that HOXB13 expression is reduced or lost in NEPCa and a loss of prostate-specific HOX code in NEPCa represents a loss of prostatic identity.

scholarly journals Posterior Hox Gene Expression and Differential Androgen Regulation in the Developing and Adult Rat Prostate Lobes

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1235-1245 ◽  
Author(s):  
Liwei Huang ◽  
Yongbing Pu ◽  
David Hepps ◽  
David Danielpour ◽  
Gail S. Prins
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Prostate Gland ◽  
Hox Gene ◽  
Expression Levels ◽  
Adult Rat ◽  
Organ Specific ◽  
Androgen Regulation ◽  
Hox Code ◽  
Rat Prostate

Axis positioning and tissue determination during development involve coordinated expression of Hox genes throughout the body. The most posterior Hox gene clusters are involved in prostate organogenesis. In the present study, we characterized and compared the expression profiles of posterior (5′) Hox genes in the separate lobes of the adult rat prostate gland, the coagulating gland, seminal vesicles, and epididymis using quantitative real-time RT-PCR. These genes include Hoxa9–11, Hoxa13, Hoxd13, and Hoxb13. We identified a unique Hox code for each of these organs and propose that this contributes to the organ-specific and prostate lobe-specific identities in the adult rat. Using the ventral prostate (VP) as a model, we characterized the Hox genes expression patterns over time from birth through adulthood. Expression levels of the three Hox13 genes and Hoxa10 were significantly higher in the adult VP compared with the neonatal developing VP suggesting an important role during adult homeostasis. In contrast, Hoxa9 and Hoxa11 levels declined after morphogenesis suggesting a specific developmental role. Overall, the Hoxb13 gene exhibited the most striking temporal and organ-specific differences. Using in situ hybridization and immunohistochemistry, a distinct Hoxb13 anterior-to-posterior expression gradient was observed with the highest expression levels in the VP luminal epithelial cells, moderate levels in the lateral prostate, and low expression in the dorsal prostate. An expression gradient was also observed along the ductal length in all three prostate lobes with strongest expression at the distal tips and limited expression in the proximal ducts. After infection with a lentivirus expressing the Hoxb13 gene, NRP-152 cells cultured under nondifferentiating conditions exhibited robust cytokeratin 8 immunostain indicating that Hoxb13 expression drives luminal cell differentiation in the rat epithelium. Androgen regulation of prostatic Hox gene expression was examined during development in vitro and after castration in the adult rat. In the neonatal VP, all six Hox genes were significantly up-regulated by androgens, whereas none of the genes were affected by testosterone in the lateral prostate. In the adult rat, castration resulted in up-regulation of Hoxa9 and Hoxa13 in the VP and down-regulation of Hoxb13 in the dorsal prostate and lateral prostate. Taken together, we conclude that the prostatic Hox genes reach a destined expression level at specific developmental time points in the prostate gland and possess differential androgenic regulation in a temporal and lobe-specific manner. We suggest that this timely Hox code participates in determining lobe-specific prostatic identity and cellular differentiation.

Homeobox genes and models for patterning the hindbrain and branchial arches

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 187-196 ◽  
Author(s):  
Paul Hunt ◽  
Jenny Whiting ◽  
Ian Muchamore ◽  
Heather Marshall ◽  
Robb Krumlauf
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Expression Pattern ◽  
Hox Genes ◽  
Homeobox Genes ◽  
Neural Plate ◽  
The Body ◽  
Hox Gene ◽  
Hox Code ◽  
Branchial Region

Antennapedia class homeobox genes, which in insects are involved in regional specification of the segmented central regions of the body, have been implicated in a similar role in the vertebrate hindbrain. The development of the hindbrain involves the establishment of compartments which are subsequently made distinct from each other by Hox gene expression, implying that the lineage of neural cells may be an important factor in their development. The hindbrain produces the neural crest that gives rise to the cartilages of the branchial skeleton. Lineage also seems to be important in the neural crest, as experiments have shown that the crest will form cartilages appropriate to its level of origin when grafted to a heterotopic location. We show how the Hox genes could also be involved in patterning the mesenchymal structures of the branchial skeleton. Recently it has been proposed that the rhombomererestricted expression pattern of Hox 2 genes is the result of a tight spatially localised induction from underlying head mesoderm, in which a prepattern of Hox expression is visible. We find no evidence for this model, our data being consistent with the idea that the spatially localised expression pattern is a result of segmentation processes whose final stages are intrinsic to the neural plate. We suggest the following model for patterning in the branchial region. At first a segment-restricted code of Hox gene expression becomes established in the neuroepithelium and adjacent presumptive neural crest. This expression is then maintained in the neural crest during migration, resulting in a Hox code in the cranial ganglia and branchial mesenchyme that reflects the crest's rhombomere of origin. The final stage is the establishment of Hox 2 expression in the surface ectoderm which is brought into contact with neural crest-derived branchial mesenchyme. The Hox code of the branchial ectoderm is established later in development than that of the neural plate and crest, and involves the same combination of genes as the underlying crest. Experimental observations suggest the idea of an instructive interaction between branchial crest and its overlying ectoderm, which would be consistent with our observations. The distribution of clusters of Antennapedia class genes within the animal kingdom suggests that the primitive chordates ancestral to vertebrates had at least one Hox cluster. The origin of the vertebrates is thought to have been intimately linked to the appearance of the neural crest, initially in the branchial region. Our data are consistent with the idea that the branchial region of the head arose in evolution before the more anterior parts, the development of the branchial region employing the Hox genes in a more determinate patterning system. In this scenario, the anterior parts of the head arose subsequently, which may explain the greater importance of interactions in their development, and the fact that Antennapedia class Hox genes are not expressed there.

scholarly journals Circuits Regulating Superoxide and Nitric Oxide Production and Neutralization in Different Cell Types: Expression of Participating Genes and Changes Induced by Ionizing Radiation

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 701 ◽  
Author(s):  
Patryk Bil ◽  
Sylwia Ciesielska ◽  
Roman Jaksik ◽  
Joanna Rzeszowska-Wolny
Keyword(s):  
Nitric Oxide ◽  
Ionizing Radiation ◽  
Cancer Cell ◽  
Superoxide Radical ◽  
Human Cancer ◽  
Cell Types ◽  
Superoxide Radicals ◽  
No Production ◽  
Specific Expression ◽  
Human Cancer Cell Lines

Superoxide radicals, together with nitric oxide (NO), determine the oxidative status of cells, which use different pathways to control their levels in response to stressing conditions. Using gene expression data available in the Cancer Cell Line Encyclopedia and microarray results, we compared the expression of genes engaged in pathways controlling reactive oxygen species and NO production, neutralization, and changes in response to the exposure of cells to ionizing radiation (IR) in human cancer cell lines originating from different tissues. The expression of NADPH oxidases and NO synthases that participate in superoxide radical and NO production was low in all cell types. Superoxide dismutase, glutathione peroxidase, thioredoxin, and peroxiredoxins participating in radical neutralization showed high expression in nearly all cell types. Some enzymes that may indirectly influence superoxide radical and NO levels showed tissue-specific expression and differences in response to IR. Using fluorescence microscopy and specific dyes, we followed the levels and the distribution of superoxide and NO radicals in living melanoma cells at different times after exposure to IR. Directly after irradiation, we observed an increase of superoxide radicals and NO coexistent in the same subcellular locations, suggesting a switch of NO synthase to the production of superoxide radicals.

scholarly journals Development of HPLC Method for Quantification of Sinigrin from Raphanus sativus Roots and Evaluation of Its Anticancer Potential

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4947
Author(s):  
Anroop B. Nair ◽  
Dipal Gandhi ◽  
Snehal S. Patel ◽  
Mohamed A. Morsy ◽  
Bapi Gorain ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Mtt Assay ◽  
Raphanus Sativus ◽  
Caspase 3 ◽  
Human Cancer ◽  
Biological Activities ◽  
Hplc Method ◽  
Human Cancer Cell Lines ◽  
Rp Hplc

Sinigrin, a precursor of allyl isothiocyanate, present in the Raphanus sativus exhibits diverse biological activities, and has an immense role against cancer proliferation. Therefore, the objective of this study was to quantify the sinigrin in the R. sativus roots using developed and validated RP-HPLC method and further evaluated its’ anticancer activity. To achieve the objective, the roots of R. sativus were lyophilized to obtain a stable powder, which were extracted and passed through an ion-exchange column to obtain sinigrin-rich fraction. The RP-HPLC method using C18 analytical column was used for chromatographic separation and quantification of sinigrin in the prepared fraction, which was attained using the mobile phase consisting of 20 mM tetrabutylammonium: acetonitrile (80:20%, v/v at pH 7.0) at a flow rate of 0.5 mL/min. The chromatographic peak for sinigrin was showed at 3.592 min for pure sinigrin, where a good linearity was achieved within the concentration range of 50 to 800 µg/mL (R2 > 0.99), with an excellent accuracy (−1.37% and −1.29%) and precision (1.43% and 0.94%), for intra and inter-day, respectively. Finally, the MTT assay was performed for the sinigrin-rich fraction using three different human cancer cell lines, viz. prostate cancer (DU-145), colon adenocarcinoma (HCT-15), and melanoma (A-375). The cell-based assays were extended to conduct apoptotic and caspase-3 activities, to determine the mechanism of action of sinigrin in the treatment of cancer. MTT assay showed IC50 values of 15.88, 21.42, and 24.58 µg/mL for DU-145, HCT-15, and A-375 cell lines, respectively. Increased cellular apoptosis and caspase-3 expression were observed with sinigrin-rich fraction, indicating significant increase in overexpression of caspase-3 in DU-145 cells. In conclusion, a simple, sensitive, fast, and accurate RP-HPLC method was developed for the estimation of sinigrin in the prepared fraction. The data observed here indicate that sinigrin can be beneficial in treating prostate cancer possibly by inducing apoptosis.

scholarly journals Targeting Human Long Noncoding Transcripts by Endoribonuclease-Prepared siRNAs

2015 ◽  
Vol 20 (8) ◽  
pp. 1018-1026 ◽  
Author(s):  
Mirko Theis ◽  
Maciej Paszkowski-Rogacz ◽  
Ina Weisswange ◽  
Debojyoti Chakraborty ◽  
Frank Buchholz
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Cost Effective ◽  
Specific Expression ◽  
Protein Coding ◽  
Human Cancer Cell Lines ◽  
Localization Analysis ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Novel Transcripts

Broad sequencing enterprises such as the FANTOM or ENCODE projects have substantially extended our knowledge of the human transcriptome. They have revealed that a large portion of genomic DNA is actively transcribed and have identified a plethora of novel transcripts. Many newly identified transcripts belong to the class of long noncoding RNAs (lncRNAs), which range from a few hundred bases to multiple kilobases in length and harbor no protein-coding potential. Although the biological activity of some lncRNAs is understood, the functions of most lncRNAs remain elusive. Tools that allow rapid and cost-effective access to functional data of lncRNAs are therefore essential. Here, we describe the construction and validation of an endoribonuclease-prepared siRNA (esiRNA) library designed to target 1779 individual human lncRNAs by RNA interference. We present a compendium of lncRNA expression data for 11 human cancer cell lines. Furthermore, we show that the resource is suitable for combined knockdown and localization analysis. We discuss challenges in sequence annotation of lncRNAs with respect to their often low and cell type–specific expression and specify esiRNAs that are suitable for targeting lncRNAs in commonly used human cell lines.

scholarly journals Regeneration-specific expression pattern of three posterior Hox genes

2003 ◽  
Vol 226 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Bea Christen ◽  
Caroline W. Beck ◽  
Aurora Lombardo ◽  
Jonathan M.W. Slack
Keyword(s):  
Expression Pattern ◽  
Hox Genes ◽  
Specific Expression ◽  
Specific Expression Pattern

Expression Profile of Selected HOX Genes in Different Childhood ALL Subtypes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4462-4462
Author(s):  
Blanka Vicenova ◽  
Ondrej Krejci ◽  
Marketa Zaliova ◽  
Katerina Muzikova ◽  
Julia Starkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profile ◽  
Hox Genes ◽  
Fusion Gene ◽  
Large Family ◽  
Poor Responders ◽  
Mrna Levels ◽  
Specific Expression ◽  
Childhood All ◽  
Hox Gene

Abstract Homeobox-containing (HOX) genes represent a large family of transcription factors that are involved in anteroposterior pattern formation during embryonic organogenesis. Besides their role in ontogenesis, various HOX genes have been associated with haematologic disorders including leukaemia. Multiple studies revealed that dysregulation of HOX genes is relevant to AML, ALL and CML; in addition, HOX genes are rearranged in some cases of human leukaemia and make part of fusion proteins such as NUP98-HOXA9, PBX1-E2A, etc. We have previously studied the pattern of HOX gene expression in chromosomally defined subsets of acute myeloid leukaemia and have shown that HOX genes exhibit a specific expression pattern throughout the AML subsets that can be related to the patient outcome. In this study, we studied the expression profile of various HOX genes in childhood acute lymphoblastic leukaemia (ALL) subtypes. We analysed mRNA levels of 23 different homeobox-containing genes in 59 children patients with ALL that were divided into six groups based on cytogenetic abnormalities and prednisone responsiveness: BCR/ABL, hyperdiploid ALL, TEL/AML1, MLL/AF4, T-ALL, prednisone good responders (PGR) and prednisone poor responders (PPR). Patient cDNA samples were analyzed using SYBRGreen I real-time quantitative PCR (qRT-PCR) and data obtained were normalized to the expression of ABL control gene. Our data indicate that certain HOX genes including HOXA3, HOXA4, HOXA5, HOXA6, HOXA9, HOXA10, HOXB2 or HOXB3 are differentially expressed throughout the ALL subtypes. Most notably, HOXA4, HOXA9, HOXB2 and HOXB3 mRNA levels appear to be elevated in T-ALL patients; hyperdiploid ALL patients display increased HOXA5 mRNA levels and HOXA3, HOXA6, HOXA9 and HOXA10 expression is higher in patients bearing the MLL/AF4 fusion gene. A relatively high level of HOXA5, HOXB2 and HOXB3 expression was observed in all patient groups. Furthermore, HOX gene expression distinguishes PGR from PPR group of patients; this divergence is most apparent in the case of HOXB2, HOXB3 and HOXB7. This study shows potential prognostic relevance of HOX gene levels in patients with childhood ALL. Data also confirm the differential HOX gene expression in various childhood ALL subtypes and underline the importance of certain HOX genes in leukemogenesis.

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