This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The present study aims at identifying proteins that are potentially involvd in prostate cancer progresion. It utilizes two sources of prostatic material: (i) the LNCaP/C4-2/C4-2B cell model of prostate cancer progression, and (ii) prostate epithelial and stromal cells from prostatectomies dichotomized by the telomeric DNA content, a marker of genomic instability. The PI has initiated the proteomic analysis of androgen-independent and non-metastatic LNCaP and their androgen-independent bone metastatic derivative C4-2 cells by using 2-dimensional liquid chromatography and iTRAQ mass spectrometry methodology. Potential biomarkers with strongly differential expression were identified, such as for example the receptor-mediated endocytosis protein 8 (RME-8), or the calcium-binding protein S100A11 (calgizzarin). Further investigations into the role and distribution of these proteins in human prostatic tissues will follow. The PI has continued to collect clinically relevant prostatic material from the Pathology Lab at UNMH and from the VA Medical Center in Albuquerque. Epithelial and stromal cells were successfully isolated from tumor and tumor-adjacent histologically normal tissue. The telomere DNA content (TC) and the extent of allelic imbalance, two markers of genomic instability, were measured in theis collection. The cells will be dichotomized by high versus low TC and analyzed by 2-dimensional liquid chromatography and iTRAQ mass spectrometry. On the professoinal development side of the proposal, it should be noted that the PI, Dr. Bisoffi, was offered a tenure-track Assistant Professorship position in the Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine. Dr. Bisoffi's project deals with aspects of prostate cancer; therefore, women are not included. The anonymous human prostic tissue is population-based, thus no specific ethnicity is targeted.
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