[Frontiers in Bioscience 14, 1945-1951, January 1, 2009]
NF-kappaB activation in breast cancer tissues

Kang-Seo Park1, Dae-Seok Kim1, Kyung-Chae Jeong1, Soo-Youl Kim1

1Molecular Oncolgy Branch, Division of Basic & Applied Sciences, Research Institute, National Cancer Center, Goyang, Kyonggi-do, 410-769, Republic of Korea

TABLE OF CONTENTS

1. Abstract
2. introduction
3..Materials and methods
3.1.Human tissue samples
3.2. Isolation of cytoplasm
3.3. Western blotting
3.4. Positive control for 814-MAM antibody recognition of GGEL linkages
3.5. TGase activity assay
3.6. Statistical Analysis
4. Results
4.1. Increase in TGase and high molecular weight protein levels in breast tumors
4.2. Depletion of free I-kBa correlates with increased TGase 2 expression in breast tumors
4.3. Increased NF-kB activity in breast tumors
4.4. Decrease in the BCl2/BAX ratio in breast tumors
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

Activation of NF-kappaB is reported in breast cancers. NF-kappaB inhibition in breast cancer cell lines results in an increase in apoptosis. However, the reason for continuous activation of this transcription factor in breast cancer is currently unclear. Interestingly, elevated transglutaminase 2 (TGase 2) expression is additionally observed in breast cancer. Recent studies showed that doxorubicin-resistant cells contain a higher level of TGase 2, compared to doxorubicin-sensitive cells. Moreover, increasing the level of TGase 2 in breast cancer cells by transient transfection leads to decreased expression of the inhibitory subunit of NF-kappaB (I-kappaBA), and up regulation of NF-kappaB activity. Our data show that TGase 2 expression is inversely correlated with the level of I-kappaBa in breast tumors, implying that the enzyme is responsible for the constitutive activation of NF-kappaB in breast tumors.