Table 1 The expression pattern of 15-LOX and its metabolites in breast cancer
From: 15-Lipoxygenase and its metabolites in the pathogenesis of breast cancer: A double-edged sword
Type of 15-LOX enzyme/ metabolites/ other mediators | Transcript/ protein level | Cell line/Human tissue type/serum | Observations | Ref |
|---|---|---|---|---|
15-LOX | mRNA | Tumor breast tissue | • Reduction of 15-LOX level in tumor tissue • Association of lower expression level with tumor stage • Lower level of 15-LOX in Lobular carcinomas | [28] |
15-LOX-1 15-LOX-2 | mRNA Protein | breast normal epithelial cells/breast tumor tissues/ vascular endothelial cells | • Tumor tissues showed lower protein level of both 15-LOX isoforms compared to breast normal/ vascular endothelial cells • Association of 15-LOX isoforms down regulation with tumor severity, recurrence, metastasis and patient’s survival • Reduction of 15-LOX-2 and no change in 15-LOX-1 in ER-positive breast tumors | [24] |
15-LOX-2 15-S-HETE | mRNA | Tumor/normal breast tissue | • High level of 15-LOX-2 transcript in normal vs tumor breast tissue • High level of 15-S-HETE in normal cells vs tumor cells • PPAR-γ mediates down-regulation of 15-LOX-2 | [30] |
Eicosanoid metabolites 15-S-HETE | Final product | Breast tumor tissues | • PGF2α, HHT and 15HETE were lower in tumors vs compared to the benign breast tumor or mammary reduction • Correlation between tumor value of 15-HETE with tumor diameter and fibrosis score | [31] |
15-LOX-2 PPAR-γ | mRNA Protein | Normal epithelial cells/ malignant breast tumor tissue | • Normal epithelial cells expressed high level of 15-LOX-2 gene and protein while low level of PPAR-γ • Malignant breast tumors/ breast (MDA453) cells low level of 15-LOX-2 and high level of PPAR-γ • breast (MCF-7 and SK-BR-3) expressed low level of 15-LOX-2 gene and protein while the level of PPAR-γ was not as high as the other malignant epithelial cells | [30] |
15-LOX | mRNA | MB231, H2380, SKBR3, T47D, ZR75, MCF-WT MCF7-adr | • SKBR3 cells was not able to express 15-LOX, while the rest of breast cancer cells expressed 15-LOX. • Dual inhibition of LOX/COX enzymes and general inhibition of LOX enzymes caused growth inhibition in SKBR3, ZR75,T47D cells. | [32] |
13-HODE, 9-HODE 13-HOTrE 9-HOTrE 12-HHTrE | Final product | Plasma of patients with breast cancer | • 13-HODE, 9-HODE, 13-HOTrE, 9-HOTrE, and 12-HHTrE were elevated in the plasma of the breast cancer patients | [33] |
13-HODE 15-HETE, 12-HETE 5-HETE 5-oxo-ETE PGD2 PGE2 | Final product | Breast tumor tissues/ breast normal tissues/ MDA-MB-231/ MCF-7 | • 13-HODE, 15-HETE, 12-HETE, 5-HETE, 5-oxo-ETE, PGD2, and PGE2 metabolites were expressed in malignant and most of normal breast tissues. • 13-HODE expression was correlated with aggressive grade and lymph node metastasis. • 13-HODE and 15-HETE induced proliferation of MDA-MB-231 and MCF-7. | [34] |