Identification of Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) as a CD8+ T-cell-defined human tumor antigen of human carcinomas

Visús, Carmen; Ito, Diasuke; Dhir, Rajiv; Szczepański, Mirosław J.; Chang, Yoo Jung; Latimer, Jean Johanna; Grant, Stephen G.; DeLeo, Albert B.

doi:10.1007/s00262-011-1001-y

Cited by 17 publications

(14 citation statements)

References 30 publications

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“…Our results demonstrating that AA but not E2 can reverse in vitro the growth inhibition of OvCa cells suggest that the role of HSD17B12 in this tumor, as in breast carcinoma, is primarily restricted to fatty acid elongation. Interestingly, the results of a similar analysis of the metabolic role of HSD17B12 in SCCHN [27] indicate that it functions in E1/E2 conversion as well as fatty acid elongation in this type of carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the development of metabolic inhibitors of this HSD17B isoform [28], it might be possible to consider HSD17B12-based immunotherapy in the future. In this regard, HSD17B12 has been identified in our laboratories as a CD8 + T cell-defined tumor antigen [27]. As a tumor cell component which is critical for cell survival and which is immunogenic (i.e., able to induce HSD17B12-specific CD8 + T cells), HSD17B12 emerges as an attractive new candidate for use in cancer vaccines against carcinomas overexpressing this enzyme.…”

Section: Discussionmentioning

confidence: 99%

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17β hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma

Szajnik

Szczepański

Elishaev

et al. 2012

Gynecologic Oncology

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Objective 17β-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in growth and progression of this tumor. Methods Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome. In A2780 OvCa cell line expressing HSD17B12, siRNA knockdown of the enzyme was performed, and its effects on tumor cell growth and Annexin V binding were determined. Results HSD17B12 expression was detected in all tumor samples, but the staining intensity was variable. Normal ovarian epithelium was negative. Patients with tumor showing weak/moderate expression of HSD17B12 had a better overall survival than those with strongly positive tumors (p<0.001). The time to first recurrence was longer for patients with tumors with heterogenous staining relative to patients with tumors that were uniformly positive (p<0.001). Upon silencing of HSD17B12 in tumor cells, their growth was inhibited (p<0.005) and apoptosis was increased (p<0.05). Arachidonic acid but not estradiol reversed the growth inhibition mediated by HSD17B12 knockdown. Conclusion HSD17B12 overexpression is shown to be a marker of poor survival in patients with OvCa. Expression in the tumor and function of this enzyme facilitates OvCa progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

17β hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma

Szajnik

Szczepański

Elishaev

et al. 2012

Gynecologic Oncology

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“…Still in this same associated window, the HSD17B12 gene is located. This gene is a member of the hydroxysteroid dehydrogenase superfamily, involved in the metabolism of steroids, retinoids, bile and fatty acids that apparently can be related in metabolic pathways involved in tumor [23]. Considering that tumor results from uncontrolled cells multiplication, it could be related to DNA repair.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study for Carcass Traits in an Experimental Nelore Cattle Population

et al. 2017

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The purpose of this study was to identify genomic regions associated with carcass traits in an experimental Nelore cattle population. The studied data set contained 2,306 ultrasound records for longissimus muscle area (LMA), 1,832 for backfat thickness (BF), and 1,830 for rump fat thickness (RF). A high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA) was used for genotyping. After genomic data quality control, 437,197 SNPs from 761 animals were available, of which 721 had phenotypes for LMA, 669 for BF, and 718 for RF. The SNP solutions were estimated using a single-step genomic BLUP approach (ssGWAS), which calculated the variance for windows of 50 consecutive SNPs and the regions that accounted for more than 0.5% of the additive genetic variance were used to search for candidate genes. The results indicated that 12, 18, and 15 different windows were associated to LMA, BF, and RF, respectively. Confirming the polygenic nature of the studied traits, 43, 65, and 53 genes were found in those associated windows, respectively for LMA, BF, and RF. Among the candidate genes, some of them, which already had their functions associated with the expression of energy metabolism, were found associated with fat deposition in this study. In addition, ALKBH3 and HSD17B12 genes, which are related in fibroblast death and metabolism of steroids, were found associated with LMA. The results presented here should help to better understand the genetic and physiologic mechanism regulating the muscle tissue deposition and subcutaneous fat cover expression of Zebu animals. The identification of candidate genes should contribute for Zebu breeding programs in order to consider carcass traits as selection criteria in their genetic evaluation.

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“…UGT2B15, in conjunction with UGT2B17, mediates glucouridination of DHT metabolites (40). HSD17B12 is a multifunctional isoenzyme functioning in the conversion of E1 to E2, and elongation of long-chain fatty acids, in particular the conversion of palmitic to archadonic (AA) acid, the precursor of sterols and the inflammatory mediator, prostaglandin E. Its over-expression together with that of COX-2 in breast carcinoma is associated with a poor prognosis (41). The rs11252845 is located in the 5′ flanking region of the AKR1C1 and may potentially be involved in the regulation of AKR1C1 expression.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Common Genetic Variations in Genes of the Sex Hormone Metabolic Pathways on Steroid Hormone Levels and Prostate Cancer Aggressiveness

Oh¹,

Jacobus²,

Regan³

et al. 2011

Cancer Prevention Research

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Background Our previous work suggested that there was no significant association between plasma steroid hormone levels and prostate cancer (CaP) tumor grade at diagnosis. In this study, we systematically tested the hypothesis that inherited variations in the androgen and estrogen metabolic pathways may be associated with plasma levels of steroid hormones, or CaP aggressiveness at diagnosis. Methods Plasma hormone levels including total testosterone, total estradiol and sex hormone-binding globulin were measured in a cohort of 508 patients identified with localized CaP. D’Amico risk classification at diagnosis was also determined. 143 single nucleotide polymorphisms (SNPs) from 30 genes that are involved in androgen and estrogen metabolism were selected for analysis. The global association of genotypes with plasma hormone levels and CaP aggressiveness (D’Amico risk classification) was statistically analyzed. Q-values were estimated to account for multiple testing. Results We observed significant associations between plasma testosterone level and SNPs in HSD17B2 (rs1424151), HSD17B3 (rs9409407) and HSD17B1 (rs12602084), with P values of 0.002, 0.006 and 0.006, respectively. We also observed borderline significant associations between prostate aggressiveness at diagnosis and SNPs in AKR1C1 (rs11252845; P = 0.005), UGT2B15 (rs2045100; P = 0.007) and HSD17B12 (rs7932905; P = 0.008). No individual SNP was associated with both clinical variables. Conclusions Genetic variants of genes in hormone metabolic pathways may influence plasma androgen levels or CaP aggressiveness. However, it appears that the inherited variations affecting plasma hormone levels differ from those affecting disease aggressiveness.

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Identification of Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) as a CD8+ T-cell-defined human tumor antigen of human carcinomas

Cited by 17 publications

References 30 publications

17β hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma

17β hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinoma

Genome-Wide Association Study for Carcass Traits in an Experimental Nelore Cattle Population

The Impact of Common Genetic Variations in Genes of the Sex Hormone Metabolic Pathways on Steroid Hormone Levels and Prostate Cancer Aggressiveness

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