Changes in steroid receptors and proteoglycan expression in the guinea pig prostate stroma during puberty and hormone manipulation.

Background: Proteoglycans are structural and informational molecules important during embryogenesis and organ maturation. Maturation of the prostate is influenced by androgens and estrogens, but changes in the relative spatiotemporal expression of steroid receptors and proteoglycans during hormonal change are unexplored.

Methods: Guinea pig prostate was used to define hormone-induced changes in the expression of androgen (AR) and estrogen (ER(alpha)) receptors, chondroitin sulfate (CS) glycosaminoglycan and core proteins of versican and syndecan-1.

Variants in the prostate-specific antigen (PSA) gene and prostate cancer risk, survival, and circulating PSA.

An A to G substitution, rs925013, in the promoter of the prostate-specific antigen gene (PSA) was recently found to be associated with promoter activity and circulating PSA levels. The objective of this study was to test the associations between rs925013 and another A to G substitution, rs266882, in the PSA gene with prostate cancer risk using a population-based case-control study of 821 prostate cancer cases and 734 controls carried out in Perth and Melbourne, Australia. The study focused on young (i.

Suppression of androgen receptor signaling in prostate cancer cells by an inhibitory receptor variant.

There is increasing evidence that sensitization of the androgen receptor (AR) signaling pathway contributes to the failure of androgen ablation therapy for prostate cancer, and that direct targeting of the AR may be a useful therapeutic approach. To better understand how AR function could be abrogated in prostate cancer cells, we have developed a series of putative dominant-negative variants of the human AR, containing deletions or mutations in activation functions AF-1, AF-5, and/or AF-2. One construct, AR inhibitor (ARi)-410, containing a deletion of AF-1 and part of AF-5 of the AR, had no intrinsic transactivation activity but inhibited wild-type AR (wtAR) in a ligand-dependent manner by at least 95% when transfected at a 4:1 molar ratio.

Exposure and binding of selected immunodominant La/SSB epitopes on human apoptotic cells.

Objective: Opsonization of apoptotic cells by autoantibodies bound to surface membrane-translocated La/SSB antigens may initiate tissue damage in the setting of congenital heart block. By injecting pregnant mice with human anti-La antibodies, we previously demonstrated the formation of IgG-apoptotic cell complexes in the developing mouse fetus; however, the binding of anti-La antibodies to human-specific epitopes could not be addressed. Accordingly, the objective of the current study was to delineate the epitope specificity of human La antibodies that are exposed on the surface of apoptotic cells.

A functional autoantibody in narcolepsy.

Narcolepsy is widely believed to have an autoimmune basis, but conventional immunological approaches have failed to detect a serum autoantibody marker. Since cholinergic hyperactivity is a feature of narcolepsy-cataplexy, we transferred IgG from nine patients with narcolepsy and nine healthy controls to mice and assessed the effect on smooth muscle contractile responses to cholinergic stimulation. IgG from all narcolepsy patients significantly enhanced bladder contractile responses to the muscarinic agonist carbachol and to neuronally released acetylcholine compared with control IgG (p<0.

Androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease.

Background: Although up to 30% of men who undergo radical prostatectomy for clinically organ-confined prostate cancer will relapse with disseminated disease, currently it is not possible to predict these patients.

Methods: Androgen receptor (AR) immunoreactivity in stromal and epithelial compartments of tumor foci was evaluated by video image analysis in 53 radical prostatectomy specimens. Kaplan-Meier and Cox Regression analyses were used to determine whether AR immunostaining was related to rate and risk of relapse, respectively.

Structural and functional consequences of glutamine tract variation in the androgen receptor.

The androgen receptor (AR) gene contains a polymorphic trinucleotide repeat region, (CAG)(n), in its N-terminal transactivation domain (NTD) that encodes a polyglutamine (polyQ) tract in the receptor protein. Whereas the length of the CAG repeat ranges from 6 to 39 in healthy individuals, the variations in repeat length both within and outside the normal range are associated with disease, including impaired spermatogenesis and Kennedy's disease, and with the risk of developing breast and prostate cancer. Whereas it has been proposed that the inverse relationship between polyQ tract length within the normal range and AR transactivation potential may be responsible for altered risk of disease, the molecular mechanisms underlying polyQ length modulation of AR function have not been elucidated.

Expression and localization of homeodomain proteins DLX4, HB9 and HB24 in malignant and benign human colorectal tissues.

Background: The purpose of this study was to identify homeobox genes expressed in the human colon and to determine whether their expression levels were altered between matched non-malignant and malignant colon tissues.

Materials And Methods: Homeobox genes expressed in colon tissue were identified by reverse transcription polymerase chain reaction (RT-PCR). Antibodies were raised to the homeodomain proteins DLX4, HB9 and HB24 and immunohistochemistry was performed on 3 moderately-differentiated tumors and their corresponding non-malignant colon tissue samples.

Expression and localization of homeodomain proteins DLX4/HB9 in normal and malignant human breast tissues.

Background: Alterations in the control of gene expression is a key event in neoplastic transformation. Investigating the expression of transcription factors such as homeodomain proteins may therefore allow better characterization of molecular mechanisms underlying the transformation process.

Materials And Methods: Expression of homeodomain proteins DLX4 and HB9 was detected by RT-PCR and immunohistochemically in 24 breast tumors and their corresponding non-malignant tissue.

ELAC2/HPC2 polymorphisms, prostate-specific antigen levels, and prostate cancer.

Background: The ELAC2 gene has been proposed to be a prostate cancer susceptibility gene and is being referred to as HPC2, in part because three case-control studies suggested that two common polymorphisms (Ser217Leu and Ala541Thr) are associated with risk. However, four subsequent larger studies have not confirmed this association. In five of the seven total studies, subject selection was influenced by prostate-specific antigen (PSA) levels.