Biomarkers of metastatic potential in cultured adenocarcinoma clones |
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Authors: | Mustafa Kh Dabbous M Margaret Jefferson Lena Haney Edwin L Thomas |
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Institution: | (1) Department of Molecular Sciences, University of Tennessee Health Science Center, 429 Boling Center, 711 Jefferson Avenue, Memphis, TN 38163, USA;(2) Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, USA; |
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Abstract: | Two-dimensional isoelectric focusing and gel electrophoresis followed by mass spectrometry were used to detect, measure, and
identify changes in protein expression correlated with differences in the metastatic potential of cultured rat mammary adenocarcinoma
cells. MTC is a non-metastatic cell clone derived from a primary tumor. MTLn2 and MTLn3 are low and high metastatic potential
cell clones derived from lung metastases of the primary tumor. A total of 1,500 proteins was detected. The patterns of protein
expression of MTLn2 and MTLn3 cells were similar. Only five spots had a threefold or greater statistically significant difference
in staining intensity between MTLn2 and MTLn3 cells, whereas 70 spots differed between MTC and MTLn3 cells. Twenty spots were
selected for further study, ten that had a positive correlation of staining intensity with metastatic potential and ten that
had a negative (inverse) correlation. Of the 17 unique proteins that were identified, five have often been cited as tumor
biomarkers. These included the positive biomarkers nucleophosmin (NPM) and 14-3-3 protein sigma and the negative biomarkers
raf kinase inhibitor protein (RKIP), peroxiredoxin-2, and galectin-1. The only identified protein that was markedly higher
in MTLn3 cells than in the less-metastatic MTLn2 cells was 14-3-3 protein sigma. The results indicate that increased metastatic
potential is associated with positive and negative changes in expression of particular proteins. Proteins that are positively
correlated with metastatic potential may prove more useful as clinical biomarkers, but those with negative correlations may
still provide useful information about underlying mechanisms of metastatic spread. |
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