Protocadherin-PC (PCDH-PC) is a gene on the human Y chromosome that is selectively expressed in apoptosis-and hormone-resistant human prostate cancer cells. The protein encoded by PCDH-PC is cytoplasmically localized and has a small serine-rich domain in its COOH terminus that is homologous to the B-catenin binding site of classical cadherins. Variants of prostate cancer cells that express PCDH-PC have high levels of nuclear B-catenin protein and increased wnt-signaling. In this study, we show that transfection of human prostate cancer cells (LNCaP) with PCDH-PC or culture of these cells in androgen-free medium (a condition that up-regulates PCDH-PC expression) activates wnt signaling as assessed by nuclear accumulation of B-catenin, increased expression of luciferase from a reporter vector promoted by Tcf binding elements and increased expression of wnt target genes. Moreover, LNCaP cells transfected with PCDH-PC or grown in androgen-free medium transdifferentiate to neuroendocrine-like cells marked by elevated expression of neuron-specific enolase and chromogranin-A. Neuroendocrine transdifferentiation was also observed when LNCaP cells were transfected by stabilized B-catenin. Increased wnt signaling and neuroendocrine transdifferentiation of LNCaP cells induced by culture in androgen-free medium was suppressed by short interfering RNAs that target PCDH-PC as well as by dominant-negative Tcf or short interfering RNA against B-catenin, supporting the hypothesis that increased expression of PCDH-PC is driving neuroendocrine transdifferentiation by activating wnt signaling. These findings have significant implications for the process through which prostate cancers progress to hormone resistance in humans. (Cancer Res 2005; 65(12): 5263-71)

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Androgen action in prostate and prostate cancer cells is dependent upon the androgen receptor (AR) protein that transcriptionally regulates the expression of androgen-dependent genes in the presence of a steroid ligand. Whereas the overall schema of androgen action mediated by this receptor protein appears to be relatively simple, androgen signaling is now known to be influenced by several other cell signal transduction pathways and here we review the evidence that the canonical Wnt signaling pathway also modulates androgen signaling at multiple levels. Wnt is a complex signaling pathway whose endpoint involves activation of transcription from LEF-1/TCF transcription factors and it is known to be involved in the development and progression of numerous human epithelial tumors including prostate cancer. beta-catenin protein, a particularly critical molecular component of canonical Wnt signaling is now known to promote androgen signaling through its ability to bind to the AR protein in a ligand-dependent fashion and to enhance the ability of liganded AR to activate transcription of androgen-regulated genes. Under certain conditions, glycogen synthase kinase-3beta (GSK-3beta), a protein serine/threonine kinase that regulates beta-catenin degradation within the Wnt signaling pathway, can also phosphorylate AR and suppress its ability to activate transcription. Finally, it was recently found that the human AR gene itself is a target of LEF-1/TCF-mediated transcription and that AR mRNA is highly upregulated by activation of Wnt signaling in prostate cancer cells. Paradoxically, Wnt activation also appears to stimulate Akt activity promoting an MDM-2-mediated degradation process that reduces AR protein levels in Wnt-stimulated prostate cancer cells. Collectively, this information indicates that the multifaceted nature of the interaction between the Wnt and the androgen signaling pathways likely has numerous consequences for the development, growth, and progression of prostate cancer.

Cotton is an important fiber crop worldwide. Improved fiber quality is a driving force for cotton genetic studies and breeding. A BC 1 population containing 115 individuals from a cross between Gossypium hirsutum cv. CCRI8 and G. barbadense cv. Pima 90-53 was established, and 519 simple sequence repeat (SSR) markers, two conserved intronscanning primers (CISPs), and transcript-derived fragments (TDFs) amplified from 156 ApoI/TaqI selective primer combinations were used to construct a genetic linkage map. The map included 579 markers distributed on 56 linkage groups. Accounting for 83.4 % of the cotton genome, it covered 4,168.72 cM, with an average distance of 7.19 cM between markers. Lengths of the linkage groups ranged from 1.25 to 255.79 cM, with 2 to 44 markers per group. Of these 56 groups, 43 were assigned to 26 chromosomes, with the remaining 13 unknown. Based on this newly constructed map of tetraploid cotton, we performed quantitative trait loci (QTL) mapping and analysis of fiber quality traits from the BC 1 and its derived BC 1 F 2 lines. A total of 44 fiber quality QTL were detected on 17 chromosomes, explaining 7.72-23.73 % of the phenotypic variation. Pima 90-53 offered 13 QTL alleles with positive additive effects and four with negative additive effects for fiber quality traits. The results from this study may provide useful information for breeders to transfer desirable fiber traits from cotton types, such as the Sea Island strain, to Upland cotton that is primarily cultivated currently.