In Vivo Quantitative Phosphoproteomic Profiling Identifies Novel Regulators of Castration Resistant Prostate Cancer Growth

In this essay, the author

• Explains that lncap xenografts mimic human prostate tumors, which proliferate at a higher rate than castration nave localized crpca. they perform phosphoproteomic profiling using silac labeled cells as internal, spiked-in controls.
• Analyzes the phosphorylation levels of 2782 peptides from a total of 1212 proteins in at least one of the samples.
• Analyzes the phosphoproteomic data of the mapk, mtorc1 pathways, and pak2 and yap1 in cr-lncap tumors.

• Explains that lncap xenografts mimic human prostate tumors, which proliferate at a higher rate than castration nave localized crpca. they perform phosphoproteomic profiling using silac labeled cells as internal, spiked-in controls.
• Analyzes the phosphorylation levels of 2782 peptides from a total of 1212 proteins in at least one of the samples.
• Analyzes the phosphoproteomic data of the mapk, mtorc1 pathways, and pak2 and yap1 in cr-lncap tumors.
• Explains that if the pathways identified as regulated in castration resistant cancer by phosphoproteomic analysis are functionally relevant, the transcriptional program of these tumors would reflect changes in mtor, akt, mapk, yap1 and pak2.
• Explains that the differential phosphorylation signaling molecules in castration resistant vs hormone sensitive tumors may be regulated by androgens.
• Explains the role of pak2 and yap1 in the growth of castration resistant prostate cancer.
• Concludes that yap1 and pak2 have overlapping functions in androgen independent prostate cancer cells that may contribute to the growth and spread of castration resistant tumors.
• Explains schroder fh, hugosson j, tammela tl, ciatto s, nelen v, et al. screening and prostate-cancer mortality in a european study.
• Analyzes the trends in prostate cancer incidence and mortality in the five nordic countries.
• Explains crawford's understanding of the epidemiology, natural history, and key pathways involved in prostate cancer.
• Explains taylor bs, schultz n, hieronymus h, gopalan a, xiao y, carver b. integrative genomic profiling of human prostate cancer
• Describes the aspects of imaging in the assessment and follow-up of benign prostatic hyperplasia.
• Explains the mutational landscape of lethal castration-resistant prostate cancer.
• Explains that in vivo amplification of the androgen receptor gene and progression of human prostate cancer.
• Describes the clinical significance of chromosome 8 alterations in high-grade, advanced, non-
• Explains the cell autonomous role of pten in regulating castration-resistant prostate cancer growth.
• Explains that reciprocal feedback regulation of pi3k and androgen receptor signaling in pten-deficient prostate cancer.
• Explains that pten deficiency is fully penetrant for prostate adenocarcinoma in c57bl/6 mice via mtor-dependent growth.
• Explains horoszewicz js, leong ss, kawinski e, karr jp, rosenthal h, chu tm, et al. lncap model of human prostatic carcinoma
• Explains that prolonging hormone sensitivity in prostate cancer xenografts through dual inhibition of ar and mtor.
• Describes stone p, richards m, a'hern r, hardy j. fatigue in patients with breast or prostate cancers undergoing radical radiotherapy.
• Explains the expression of basal cell keratins in human prostate cancer metastases and cell lines.
• Explains pelttari lm, nurminen r, gylfe a, aaltonen la, schleutker j, nevanlinna h. screening of finnish rad51c founder mutations
• Explains the early biochemical outcomes following permanent interstitial brachytherapy as monotherapy in 1050 patients with clinical t1-t2 prostate cancer.
• Describes thalmann gn, anezinis pe, chang sm, zhau he, kim ee, hopwood vl, et al. androgen-independent cancer progression and bone metastasis in the lncap model of human prostate cancer.
• Explains that multipotent stromal cell therapy for cavernous nerve injury-induced erectile dysfunction.
• Evaluates the sexual and voiding function after total mesorectal excision with pelvic autonomic nerve preservation in males with rectal cancer.
• Explains that differentially expressed transcripts in neoplastic hepatic nodules and neonatal rat liver were studied by cdna microarray analysis.
• Explains that few fh mutations in sporadic counterparts of tumor types observed in hereditary leiomyomatosis and renal cell cancer families.
• Explains the correlation between transrectal ultrasound and histopathology of radical prostatectomy specimens.
• Explains sedelaar, de la rosette, beerlage, wijkstra, and aarnink. transrectal ultrasound imaging of the prostate: review and perspectives of recent developments.
• Explains harvey kf, zhang x, thomas dm. the hippo pathway and human cancer.
• Explains that the small-molecule p21-activated kinase inhibitor pf-3758309 inhibits oncogenic signaling and tumor growth.
• Explains that human prostate cancer blocks the generation of dendritic cells from cd34+ hematopoietic progenitors.
• Explains that genetic and pharmacological disruption of the tead-yap complex suppresses the oncogenic activity of yap.
• Explains that roberts pj and der cj target the raf-mek-erk mitogen-activated protein kinase cascade for the treatment of cancer.
• Explains that dd3(pca3) is a sensitive and specific marker to detect prostate tumors. cancer research. 2002;62(9):2695-8.
• Explains that the deficiency of akt1 is sufficient to suppress tumor development in pten+/- mice.
• Explains the effect of transurethral needle ablation on symptoms of chronic pelvic pain syndrome.
• Explains that cell detachment activates the hippo pathway via cytoskeleton reorganization to induce anoikis.
• Describes d'antonio jm, ma c, monzon fa, pflug br. longitudinal analysis of androgen deprivation of prostate cancer cells identifies pathways
• Explains that high stromal hyaluronan level is associated with poor differentiation and metastasis in prostate cancer.
• Analyzes the quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues.
• Explains that timp-1 increases expression and phosphorylation of proteins associated with drug resistance in breast cancer cells.
• Explains olsen jv, schwartz jc, griep-raming j, nielsen ml, damoc e, denisov e. a dual pressure linear ion trap orbitrap instrument with very high sequencing speed.
• Explains that the phytoestrogen equol stimulates the transcriptional activity of estrogen-related receptor gamma.
• Explains that androgen induction of prostate cancer cell invasion is mediated by ezrin.
• Explains that pharmacological inhibition of yap1 and pak2 may serve to inhibit crpca tumor growth using pre-clinical models.
• Explains that the ndc80 internal loop is required for recruitment of the ska complex to establish end-on microtubule attachment to kinetochores.