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Molecular alterations in primary prostate cancer after androgen ablation therapy

Title: Molecular alterations in primary prostate cancer after androgen ablation therapy
Authors: Best, CJM; Gillespie, JW; Yi, YJ; Chandramouli, GVR; Perlmutter, MA; Gathright, Y; Erickson, HS; Georgevich, L; Tangrea, MA; Duray, PH; Gonzalez, S; Velasco, A; Linehan, WM; Matusik, RJ; Price, DK; Figg, WD; Emmert Buck, MR; Chuaqui, RF
Publisher Information: AMER ASSOC CANCER RESEARCH
Publication Year: 2024
Collection: Pontificia Universidad Católica de Chile: Repositorio UC
Subject Terms: GENE-EXPRESSION ANALYSIS; LASER CAPTURE MICRODISSECTION; CDNA MICROARRAY ANALYSIS; DEPRIVATION THERAPY; NEUROENDOCRINE DIFFERENTIATION; TUMOR ANGIOGENESIS; ALLELIC LOSS; CELL-LINES; BCL-X; GROWTH; 03 Good Health and Well-being; 03 Salud y bienestar
Description: Purpose: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent Samples from primary and-metastatic sites. ; Experimental Design: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering', and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping. ; Results: Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors-macromolecule biosynthesis was clown-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p2l, 6p2l, 8p2l, 11p15, 11q12,12q23,16q12, and 16q2l. ; Conclusions: Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the devellopment,of targeted therapeutic intervention. ; DIVISION OF BASIC SCIENCES - NCI ; DIVISION OF CLINICAL SCIENCES - ...
Document Type: article in journal/newspaper
File Description: 12 páginas; application/pdf
Language: English
Relation: MEDLINE:16203770; https://repositorio.uc.cl/handle/11534/78469; WOS:000232238100013
DOI: 10.1158/1078-0432.CCR-05-0585
Availability: https://repositorio.uc.cl/handle/11534/78469; https://doi.org/10.1158/1078-0432.CCR-05-0585
Rights: acceso restringido
Accession Number: edsbas.90F14037
Database: BASE