Prostate cancer phosphorylation

In a recent study, LNCaP and PC3 prostate cancer cells treated with lycopene-based agents have been reported to undergo mitotic arrest. Lycopene s antiproliferative effects were likely achieved through a block in Gl/S transition mediated by decreased levels of cyclins D1 and E and cyclin-dependent kinase4 and suppressed retinoblastoma phosphorylation (Ivanov et al., 2007). 

Choi YH, Kang HS, Yoo MA. (2003) Suppression of human prostate cancer cell growth by betalapachone via down-regulation of pRB phosphorylation and induction of Cdk inhibitor p21(WAFl/CIPl). J Biochem Mol Biol 36 223-229. 

Haidar S, Chintapalli J, Croce CM. Taxol induces Bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 1996 56(6) 1253-1255. 

Anazawa Y, Nakagawa H, Furihara M, Ashida S, Tamura K, Yoshioka H, et al. PCOTH, a novel gene overexpressed in prostate cancers, promotes prostate cancer cell growth through phosphorylation of oncoprotein TAF-Ibeta/SET. Cancer Res 2005 65(11) 4578-4586. 

A reduction in IGF levels could be beneficial in prostate cancer treatment. Administration of the LH-RH antagonist, Cetrorelix, caused a reduction in IGF-I serum levels and tumor IGF-II levels in nude mice transfected with PC-3 cells (LI). Zoladex, a LH-RH agonist with antimitogenic activity, caused a decrease in IGF-I as well as IGFRI levels in DU-145 cells (M9). In the latter case, phosphorylation of IGFRI was prevented, causing a further inhibitory role of IGFRI action. 

The SI LAC approach has also been used to investigate metastatic prostate cancer development at the protein level (Everley et al., 2004). The fact that proteins showed altered concentration ratios by quantitative MS was confirmed by western blotting. In addition, proteomic approaches for quantitation of protein phosphorylation via SILAC combined with MS analysis have been described (Gruhler et al., 2005 Ibarrola et al., 2003, 2004). A recent study reports on identification as well as relative quantitation of in vivo mefhylation sites of proteins in HeLa cells by stable isotope labeling wifh C Hj-methionine (Ong et al., 2004). 

Figure 3 MS/MS spectrum of the phosphopeptide FNDS EGDDTEETEDYR. The spectrum, which was acquired with an ion trap mass spectrometer, illustrates the typical behavior of phosphopeptide ions under low-energy CID. The molecular ion was (M- -2EI)2+, m/z 1001.9. The MS/MS spectrum is dominated by an intense product ion corresponding to the neutral loss of phosphoric acid from the activated precursor ion. In addition, the spectrum contains a number of product ions from the y- and b-series that determine the peptide sequence and the site of phosphorylation. (The product ions are singly charged unless noted otherwise). This phosphopeptide belongs to Bcl-2-associated transcription factor 1 (BCEFI HUMAN) and it was identified in the analysis of the phosphoproteome in the LNCaP prostate cancer cell line.

In human breast and prostate cancer cell fines, retinoids have been shown to induce apoptosis via induction of p21/ WAF/cipl (Thompson et al., 1996 Li et al., 1996) and affect G1 cell cycle arrest through mitogen-activated protein kinase phosphorylation (Nakagawa et al., 2003). Zhang and Rosdahl (2005) demonstrated that expression of Idl protein decreased and that of pi6 protein increased in melanoma cell fines exposed to all-rntwr-RA, and suggested that these alterations may be involved in the observed apoptosis and cell cycle redistribution. 

Low levels (0.1-1 pg/mL) of resveratrol have been reported to enhance cell proliferation, whereas higher amounts (10-100 pg/mL) cause apoptosis in a vari-ety of tumor and endothelial cells, including JB6 epidermal cells, human promyeloctye leukemia HL-60 cells, THP-1 human monocytic leukemia cells, U937 human promonocytic cells, various colon cancer cell lines, human mammary cancer cell lines, and human prostate cancer cells [121-131]. In somewhat of a contrast to these studies, a very recent report indicated that resveratrol reduced paclitaxel-induced apoptosis in a human neuroblastoma cell line (SH-SY5Y) by blocking paclitaxel-induced phosphorylation of JNKs, Raf-1, and BcT2 [132]. Of particular interest is a recent study in which it was shown to induce apoptosis in leukemic human lymphocytes but, under similar conditions, had no effect on the survival... 

Lin HY, Shih A, Davis FB, Tang HY, Martino LJ, Bennett JA, Davis PJ. Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line. J Urol 2002 168 748-755. 

If cancerous lesions are not growing rapidly, they do not metabolize glucose avidly, and are often not visible by PET/FDG imaging. These include prostate cancer, bronchio-alveolar lung cancer, early stages of breast cancer, and renal cancer. They do accumulate C-11 acetate, which reflects oxidative phosphorylation (Krebs cycle)), and C-11 or F-18 labeled choline, a constituent of biological membranes. 

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