Contribution of HSD17B12 for estradiol biosynthesis in human breast cancer
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ABSTRACT: 17beta-hydroxysteroid dehydrogenase type12 (HSD17B12) has been demonstrated to be involved in regulation of in situ biosynthesis of estradiol (E2). HSD17B12 expression was reported in breast carcinomas but its functions have remained unknown. Therefore, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases in order to analyze an association of the enzyme expression with intratumoral E2 production. No significant correlations were detected between intratumoral HSD17B12expression and E2 concentration.These findings suggest that the presence of HSD17B12 in carcinoma cells contributes to a development of human breast carcinoma via a pathway other than in situ E2 biosynthesis. Gene expression profiles of LCM samples in isolated carcinoma cells in 16 breast carcinoma cases were examined using microarray analysis. Breast carcinomas were rapidly embedded in Tissue-Tek optimal cutting temperature compound (Sakura Finetechnical Co. Ltd., Tokyo, Japan) and frozen sectioned at a thickness of 8micro m. Approximately 5000 cells were laser transferred from these isolated specimens. Isolated total RNA was applied microarray analysis. Sample preparation and processing were performed essentially as described in the Affymetrix GeneChip Expression Analysis Manual (Affymetix, Inc., Santa Clara, CA). The labeled cRNA samples were hybridized to the complete human U133 GeneChip set (Affymetrix), including 22,215 and 22,577 genes. In our present study, we focused on mRNA expression of 156 genes which is annotated according to Gene Ontology database (steroid biosynthetic process, accession No.6694) as genes involved in steroid biosynthesis, and HSD17B12 unregistered in Gene Ontology accession No.6694. The gene expression profiles of the patients with breast cancer in which tissue estradiol was under detection limit (2 patients) was averaged, and applied to an analysis. 15 gene expression profiles of 16 breast carcinomas examined were arranged according to the levels of tissue estradiol concentration, and the clustering analysis between each gene was performed using GeneSpring GX 7.3.1 (Agilent Technologies, Waldbronn, Germany).
ORGANISM(S): Homo sapiens
SUBMITTER: Shuji Nagasaki
PROVIDER: E-GEOD-11965 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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