Biomedical subjects

Kulkarni Prakash

Publications and source records attributed to Kulkarni Prakash.

4 recordsLinked to original sources

PubMed2004

Increased expression of CYR61, an extracellular matrix signaling protein, in human benign prostatic hyperplasia and its regulation by lysophosphatidic acid.

Lysophosphatidic acid (LPA) is an endogenous lipid growth factor that is thought to play important roles in cell proliferation and antiapoptosis and therefore may have roles in the development and progression of benign prostatic hyperplasia (BPH). CYR61 (CCN1), on the other hand, is a growth factor-inducible immediate early gene that functions in cell proliferation, differentiation, and extracellular matrix synthesis. Here we show the close relationship between LPA-induced expression of CYR61 and prostate enlargement. CYR61 mRNA and protein were dramatically up-regulated by 18:1 LPA (oleoyl-LPA) within 1 and 2 h, respectively, in both stromal and epithelial prostatic cells. G protein-coupled receptors, i.e. Edg-2, Edg-4, and Edg-7, for LPA were also expressed in both stromal and epithelial prostatic cells. Furthermore, on DNA microarray analysis for normal and BPH patients, CYR61 was found to be related to the development and progression of BPH, regardless of symptoms. Although CYR61 mRNA was synthesized in hyperplastic epithelial cells, in many cases of BPH, CYR61 protein was detected in both the epithelial and stromal regions of BPH patient tissues. The functional contribution of CYR61 to prostatic cell growth was demonstrated by recombinant CYR61 protein and anti-CYR61 neutralizing antibodies, which inhibited CYR61-dependent cell spreading and significantly diminished cell proliferation, respectively. In conclusion, these data support the hypothesis that LPAs induce the expression of CYR61 by activating G proteincoupled receptors and that CYR61 acts as a secreted autocrine and/or paracrine mediator in stromal and epithelial hyperplasia, demonstrating the potential importance of this signaling mechanism in the disease.

Aged↗

PubMed2003

Development of quantitative detection assays for CYR61 as a new marker for benign prostatic hyperplasia.

Among urological diseases, benign prostatic hyperplasia (BPH) exhibits a high morbidity rate, afflicting approximately 50% of men older than age 50 years. Despite intense research efforts over the past decades, the etiology and mechanisms of BPH progression are only poorly understood. Employing oligonucleotide microarrays, the authors analyzed the gene expression profiles in normal and BPH prostate samples and found that CYR61, an immediate early gene, is markedly overexpressed in BPH. To quantify cellular CYR61 mRNA expression directly, the authors developed an assay using branched-chain DNA (bDNA) technology. A human prostatic epithelial cell line, BRF-55T, derived from a BPH patient, was treated with fetal bovine serum to stimulate gene expression, and then the induction profile of the CYR61 mRNA in these serum-stimulated cells was quantitated using both bDNA and quantitative reverse transcriptase-PCR (RT-PCR). The results obtained with the 2 detection systems were found to be very similar. The bDNA assay was also found to be sensitive and highly reproducible. To the authors' knowledge, this is the first time that identifying CYR61 as a novel marker for BPH and its quantitation has been reported. These detection methods not only may be useful for diagnostic purposes but may also be used to identify suppressors of CYR61 expression for BPH therapy employing high-throughput screening assays.

Animals↗

PubMed2002

Symptomatic and asymptomatic benign prostatic hyperplasia: molecular differentiation by using microarrays.

Benign prostatic hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed by using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not seem to change with age. These data could provide novel approaches for alleviating symptoms and hyperplasia in BPH.

Adolescent↗

PubMedDate not supplied

Androgen regulation of JM-27 is associated with the diseased prostate.

Despite intense research efforts, the etiology of prostatic hyperplasia associated with both benign prostatic hyperplasia (BPH) and prostate cancer remains poorly understood. Our previous studies using array technology identified JM-27 as a transcript that is dramatically up-regulated in the prostates of patients with symptomatic BPH and in normal, adjacent prostatic regions of patients with prostate cancer. In the present study, using an extended sample set, we show a correlation between the messenger RNA and protein expression of JM-27. To investigate the possible functions of this gene, its expression in the rat prostate was examined by immunoblot analysis using a polyclonal antibody specific to human JM-27. This antibody reacts with 2 rat polypeptides of 17 kd and 27 kd in size. Whereas the 27-kd form of the JM-27 protein found in human prostate is selectively expressed in the dorsolateral lobes of the rat prostate, the 17-kd form is expressed only in the ventral lobe. Expression of both forms of this protein appears to be androgen-regulated. There is a time-dependent decrease in expression of the protein products in the ventral and dorsolateral lobes of the rat prostate after castration. Administration of exogenous testosterone in castrated animals maintains protein expression in both lobes. Androgens are believed to play a central role in prostate growth and development, and therefore, it is tempting to speculate that JM-27, an androgen-regulated gene, may be involved in prostatic growth regulation. Further studies are underway to evaluate such a function for JM-27 in prostatic diseases.

Animals↗