Aldehyde Dehydrogenase 1 and Raf Kinase Inhibitor Protein Expression Defines the Proliferative Nature of Cervical Cancer Stem Cells
Purpose: To determine the differences in response following the use of aldehyde dehydrogenase 1 (ALDH1) and Raf kinase inhibitor protein (RKIP) as cervical cancer stem cell markers.
Methods: To evaluate the cancer stem cell markers, a mouse model with low and high grade cervical cancer was developed and studied by histological examination. Immunohistochemical and Western blotting techniques were employed to study the expression profiles of ALDH1 and RKIP. The specificity of Sox2 that determines cancer stem cells served as control to validate ALDH1 and RKIP expressions.
Results: Histological data helped to differentiate low from high grade cervical cancer. The results from immunohistochemistry show increased pattern of Sox2 expression as tumour progresses. Similarly, ALDH1, a protein that positively regulates stem cells shows mild expression in low grade cervical tumour, but positive signals are more amplified in an aggressive stage of tumour condition when compared with Sox2. The expression study with RKIP, a protein that negatively regulates stem cells, interestingly defines the higher expression in low grade cervical cancer to regulate the tumour, but shows little or no very mild expression in the aggressive stage of tumour. All the data obtained show a statistically significant value of p < 0.05. The results with Immunohistochemistry were further validated using the western blotting analysis and it also confirms the similar results.
Conclusion: ALDH1 and RKIP marker in association correlation with Sox2 aids in defining the proliferative ability of cervical cancer stem cells and also to validate them in initial and advanced stages of cervical cancer.
Keywords: Cervical cancer, ALDH1, BALB/c-nu/nu, HeLa cells, RKIP, Sox2