Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty

Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland at puberty, a crucial juncture in prostate development that is androgen dependent. Understanding the role played by androgens in normal prostate development may provide greater insight into androgen involvement in prostatic diseases. Benign prostate tissues obtained from pubertal and adult age group cadaveric organ donors were harvested and profiled using 20,000 element cDNA microarrays. Statistical analysis of the microarray data identified 375 genes that were differentially expressed in pubertal prostates relative to adult prostates including genes such as Nkx3.1, TMEPAI, TGFBR3, FASN, ANKH, TGFBR2, FAAH, S100P, HoxB13, fibronectin, and TSC2 among others. Comparisons of pubertal and BPH expression profiles revealed a subset of genes that shared the expression pattern between the two groups. In addition, we observed that several genes from this list were previously demonstrated to be regulated by androgen and hence could also be potential in vivo targets of androgen action in the pubertal human prostate. Promoter searches revealed the presence of androgen response elements in a cohort of genes including tumor necrosis factor‐α induced adipose related protein, which was found to be induced by androgen. In summary, this is the first report that provides a comprehensive view of the molecular events that occur during puberty in the human prostate and provides a cohort of genes that could be potential in vivo targets of androgenic action during puberty.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154303/1/fsb2fj042415fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154303/2/fsb2fj042415fje-sup-0001.pd

Isolation and characterization of a transforming growth factor-β\beta Type II receptor cDNA from Xenopus laevis

Transforming Growth Factor-$\beta$ $(TGF-\beta)$ and their receptors have been characterized from many organisms. Two $TGF-\beta$ signaling receptors called Type I and II have been described for various ligands of the superfamily from organisms ranging from Drosophila to humans. In Xenopus laevis, $TGF-\beta 2$ and 5 have been reported and presumably, play important roles during early development. Several Type I and type II receptors for many ligands of the $TGF-\beta$ superfamily except $TGF-\beta$ type II receptor $(T \beta IIR)$, have been characterized in Xenopus laevis. A chemical cross linking experiment using iodinated $TGF-\beta 1$ and -$\beta 5$, revealed four specific binding proteins on XTC cells. In order to understand the $TGF-\beta$ involvement during Xenopus development, a $TGF-\beta$ type II receptor $(XT \beta IIR)$ has been isolated from a XTC cDNA library. $XT \beta IIR$ was a partial cDNA lacking a portion of the signal peptide. The sequence analysis and homology comparison with the human $T\beta IIR$ revealed 67% amino acid similarity in the extra cellular domain, 60% similarity in the transmembrane domain and 87% similarity in the cytoplasmic kinase domain, suggesting that $XT \beta IIR$ is a putative $TGF-\beta$ type II receptor. In addition, the consensus amino acid motif for serine threonine receptor kinases was also present. Further, a dominant negative expression construct lacking the cytoplasmic kinase domain (engineered with the signal peptide from human $TGF-\beta$ type II receptor), was able to abolish $TGF-\beta$ mediated induction of a luciferase reporter plasmid, in a transient cell transfection assay. This substantiates the notion that $XT \beta IIR$ cDNA can act as a receptor for $TGF-\beta$. RT-PCR analysis using RNA isolated from various developmental stages of Xenopus laevis revealed expression of this gene in all the early stages of development and in the adult organs, except in stages 46/48

ProTrack: An Interactive Multi‐Omics Data Browser for Proteogenomic Studies

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive multi‐omics data resources of deep proteogenomic profiles for multiple cancer types. To enable the broader community of biological and medical researchers to intuitively query, explore, and download data and analysis results from various CPTAC projects, a prototype user‐friendly web application called “ProTrack” is built with the CPTAC clear cell renal cell carcinoma (ccRCC) data set (http://ccrcc.cptac-data-view.org). Here the salient features of this application which provides a dynamic, comprehensive, and granular visualization of the rich proteogenomic data is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/2/pmic13304.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/1/pmic13304_am.pd

ProTrack: An Interactive Multi‐Omics Data Browser for Proteogenomic Studies

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) initiative has generated extensive multi‐omics data resources of deep proteogenomic profiles for multiple cancer types. To enable the broader community of biological and medical researchers to intuitively query, explore, and download data and analysis results from various CPTAC projects, a prototype user‐friendly web application called “ProTrack” is built with the CPTAC clear cell renal cell carcinoma (ccRCC) data set (http://ccrcc.cptac-data-view.org). Here the salient features of this application which provides a dynamic, comprehensive, and granular visualization of the rich proteogenomic data is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/2/pmic13304.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163654/1/pmic13304_am.pd