Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have utilized the technique of lectin-loading of SDS gels with iodinated concanavalin A and wheat germ agglutinin to identify glycoproteins in prostatic and seminal fluids as well as in prostate tissue fractions. The following subunits which bound both lectins were detected: (a) 50, 43 and 38 kDa subunits common to prostatic and seminal fluids, and an additional 55 kDa subunit which predominates only in prostatic fluid; (b) 78, 55, 50 and 43 kDa subunits in prostatic tissue cytosol and (c) 195, 170, 135, 116 and 95 kDa subunits present in the particulate fractions of prostatic tissue. Immunoblotting using specific rabbit antibodies revealed the 50 kDa band to be prostatic acid phosphatase and the 38 kDa band to be prostate-specific antigen. Interestingly, antibodies directed toward prostatic acid phosphatase were found to cross-react with the 43 kDa band. Fractionation on sucrose gradients showed that several of these particulate glycoproteins were associated with a vesicle fraction enriched in adenylate cyclase activity, implying that they are plasma membrane glycoproteins. Comparison of soluble and particulate fractions of normal and cancerous tissue homogenates was made by densitometric scanning of autoradiograms of lectin-loaded gels. Similar relative intensities of lectin-binding were obtained for corresponding proteins in normal and cancerous tissue fractions. Also, immunoblotting showed no differences in prostatic acid phosphatase or prostate-specific antigen between normal and cancerous soluble homogenate fractions. Our results suggest that major lectin-binding proteins are conserved in the transition from normal to cancerous tissue. These results may be useful in developing a multiple-marker profile of metastatic prostate cancer and for the design of imaging agents, such as monoclonal antibodies, to prominent soluble and particulate prostate glycoproteins.
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PMID:Identification of structural and secretory lectin-binding glycoproteins of normal and cancerous human prostate. 639 53

These experiments were designed to examine the relationship between the effects of steroid hormones mediated by classic intracellular steroid hormone receptors and those mediated by a signaling system subserved at the plasma membrane by a receptor for sex hormone-binding globulin. It is known that unliganded sex hormone-binding globulin (SHBG) binds to a receptor (RSHBG) on prostate membranes. The RSHBG.SHBG complex is rapidly activated by estradiol to stimulate adenylate cyclase, with a resultant increase in intracellular cAMP. In this paper we examine the effect of this system on a prostate gene product known to be activated by androgens, prostate-specific antigen. In serum-free organ culture of human prostates, dihydrotestosterone caused an increase in prostate specific antigen secretion. This event was blocked by the anti-androgens cyproterone acetate and hydroxyflutamide. In the absence of androgens, estradiol added to prostate tissue, whose RSHBG was occupied by SHBG, reproduced the results seen with dihydrotestosterone. Neither estradiol alone nor SHBG alone duplicated these effects. The estradiol.SHBG-induced increase in prostate-specific antigen was not blocked by anti-estrogens, but was blocked both by anti-androgens and a steroid (2-methoxyestradiol) that prevents the binding of estradiol to SHBG. Furthermore, an inhibitor of protein kinase A prevented the estradiol.SHBG-induced increase in prostate-specific antigen but not that which followed dihydrotestosterone. These data indicate that there is a signaling system that amalgamates steroid-initiated intracellular events with steroid-dependent occurrences generated at the cell membrane and that the latter signaling system proceeds by a pathway that involves protein kinase A.
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PMID:Estradiol activates the prostate androgen receptor and prostate-specific antigen secretion through the intermediacy of sex hormone-binding globulin. 905 66

The molecular mechanisms involved in differentiation of prostate cancer cells to a neuroendocrine (NE) cell phenotype are not well understood. Here we used the androgen-dependent human prostate cancer cell line LNCaP to perform a systematic and broad analysis of the expression, pharmacology, and functionality of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP) receptors. Reverse transcription polymerase chain reaction experiments, together with pharmacological approaches with a set of specific agonists and antagonists, demonstrated the presence of the three VIP/PACAP receptor subtypes (PAC1, VPAC1, and VPAC2 with a major role for VPAC1, acting through adenylate cyclase (AC) stimulation. An essentially similar pattern was observed by NE differentiated cells (4 days after serum deprivation) in spite of the important morphological changes observed. However, the expression of the prostate-specific antigen (PSA) decreased in NE cells (and increased again by dihydrotestosterone, DHT, treatment). The present demonstration of the induction of NE transdifferentiation in LNCaP cells by increasing concentrations of VIP adds value to previous observations on the role of cAMP in this process, an interesting topic in the comprehension of the molecular changes that are involved in the progression of prostate cancer to androgen independence.
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PMID:Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors. 1172 28