Optical Redox Imaging Detects the Effects of DEK Oncogene Knockdown on the Redox State of MDA-MB-231 Breast Cancer Cells.

Abstract

PURPOSE:

Optical redox imaging (ORI), based on collecting the endogenous fluorescence of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) containing a redox cofactor flavin adenine dinucleotide (FAD), provides sensitive indicators of cellular metabolism and redox status. ORI indices (such as NADH, FAD, and their ratio) have been under investigation as potential progression/prognosis biomarkers for cancer. Higher FAD redox ratio (i.e., FAD/(FAD + NADH)) has been associated with higher invasive/metastatic potential in tumor xenografts and cultured cells. This study is to examine whether ORI indices can respond to the modulation of oncogene DEK activities that change cancer cell invasive/metastatic potential.

PROCEDURES:

Using lentiviral shRNA, DEK gene expression was efficiently knocked down in MDA-MB-231 breast cancer cells (DEKsh). These DEKsh cells, along with scrambled shRNA-transduced control cells (NTsh), were imaged with a fluorescence microscope. In vitro invasive potential of the DEKsh cells and NTsh cells was also measured in parallel using the transwell assay.

RESULTS:

FAD and FAD redox ratios in polyclonal cells with DEKsh were significantly lower than that in NTsh control cells. Consistently, the DEKsh cells demonstrated decreased invasive potential than their non-knockdown counterparts NTsh cells.

CONCLUSIONS:

This study provides direct evidence that oncogene activities could mediate ORI-detected cellular redox state.

• Authors: Yu Wen, He N Xu, Lisa Privette Vinnedge, Min Feng, Lin Z Li
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 21 Issue 3 Pg. 410-416 (06 2019) ISSN: 1860-2002 [Electronic] United States
• PMID: 30758703 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chromosomal Proteins, Non-Histone
• DEK protein, human
• Oncogene Proteins
• Poly-ADP-Ribose Binding Proteins

Topics

• Breast Neoplasms (diagnostic imaging, metabolism, pathology)
• Cell Line, Tumor
• Chromosomal Proteins, Non-Histone (genetics)
• Female
• Gene Knockdown Techniques
• Humans
• Neoplasm Invasiveness
• Oncogene Proteins (genetics)
• Oncogenes
• Optical Imaging
• Oxidation-Reduction
• Poly-ADP-Ribose Binding Proteins (genetics)