Preferential expression of IGF-1Ec (MGF) transcript in cancerous tissues of human prostate: Evidence for a novel and autonomous growth factor activity of MGF E peptide in human prostate cancer cells

BACKGROUND. By alternative splicing the IGF-1 gene produces several different transcripts, including IGF-1Ec (MGF). The latter has been mainly associated with muscle regeneration processes. METHODS. We used immunohistochemistry, RT-PCR, and Western analysis to show the expression status of MGF in prostate tissue and human prostate cell lines (HPrEC, PC-3, and LNCaP) and we studied the exogenous administration of the MGF peptide E on cellular proliferation using trypan blue and MTT assays, before and after the silencing of the IGF-1 receptor and insulin receptor (siRNA methods). The MGF-induced intracellular activation was examined by Western analysis of the active forms of ERK1/2 and Akt. RESULTS. We documented that MGF is overexpressed in human prostate cancer (PCa) tissues and in human PC-3 and LNCaP cells. Notably, MGF expression was remarkably higher in PCa and prostatic intraepithelial neoplasia (PIN) than normal prostate tissues, while the normal prostate epithelial cells (HPrEC) did not express MGF. Exogenous administration of a synthetic MGF E peptide stimulated the PCa cell growth and activated ERK1/2 phosphorylation without affecting Akt phosphorylation. IGF-1R or insulin receptor (IR) silencing did not affect the mitogenic activity and intracellular signaling of the MGF E peptide in these PCa cells. CONCLUSIONS. These data suggest the possible implication of MGF E peptide in cancer biology, implying a preferential MGF expression in PCa tissues and cells. This preferential IGF-1 mRNA expression generates the MGF E peptide that possesses mitogenic activity through mechanisms independent of IGF-1R, IR, and hybrid IGF-1R/IR. © 2010 Wiley-Liss, Inc

Detection of the circulating tumor cells in cancer patients

As the presence of tumor cells circulating in the blood is associated with systemic disease and shortened survival, the establishment of a method to detect circulating tumor cells (CTCs) is of critical importance for a more concise staging and follow-up of cancer patients. Recently, the most robust strategies for the determination of CTCs are the PCR-based methods and the CellSearch ® system that exploits the immunofluorescent characterization and isolation of cancer cells. Herein, we analyzed the experimental strategies used for determining CTCs with respect to accuracy, sensitivity and reproducibility in cancers of the breast, colon, prostate and melanoma. © 2010 Future Medicine Ltd

Combined androgen blockade therapy can convert RT-PCR detection of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts from positive to negative in the peripheral blood of patients with clinically localized prostate cancer and increase biochemical failure-free survival after curative therapy

Background: The clinical relevance of positive molecular staging as defined by reverse transcriptase-polymerase chain reaction (RT-PCR) detections of both prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts in the peripheral blood (PB) of patients with prostate cancer is still debatable. Methods: We analyzed the biochemical failure-free survival (bFFS) of prostate cancer patients with positive molecular staging who underwent immediate curative therapy (Group I, n=39) compared to prostate cancer patients who did convert their positive molecular staging by the administration of combined androgen blockade (CAB) for 12 months prior to curative treatment (Group II, n=15). Results: The median bFFS for Group I was 9 months (95% CI 5-13 months) and was significantly lower compared to Group II (>36 months, p<0.001). In Group I, the median time for PSA values of >2.0 ng/mL was 18 months (95% CI 12-21 months, range 12-36 months). Notably, only one patient from Group II reached PSA values >2.0 ng/mL at 36 months post-curative treatment. Conclusions: In patients with clinically localized prostate cancer and positive RT-PCR detection of PSA and PSMA transcripts in PB, CAB can convert positive molecular staging status to negative and by doing so it modifies the post-curative therapy bFFS of patients with clinically localized prostate cancer. © 2007 by Walter de Gruyter