engleski

Elevated levels of expression of TCF-1 and LEF-1 transcription factors in astrocytic brain tumors

Wnt signaling pathway that was discovered 30 years ago has today been proved to be one of the basic cellular pathways whose misregulation plays important roles in tumorigenesis. Central mediators of transcription of this pathway are members of TCF/LEF (T-cell factor/lymphoid-enhancing factor) transcription factor family. The human TCF/LEF family consists of four proteins, TCF-1 (TCF7), TCF-3 (TCF7L1), TCF-4 (TCF7L2) and LEF-1. The work presented in this paper focused on the levels and changes of expression of two members of TCF/LEF family, TCF-1 and LEF-1 in a set of astrocytic brain tumors. Glioblastomas were characterized with strong TCF-1 expression in 51.6% of samples and with strong LEF-1 expression in 71% of samples. Astrocytoma grade I showed almost opposite expression levels with weak or no expression in the 63.2% for TCF-1 and 68.2% for LEF-1. Statistical analysis additionally confirmed significant differences in protein expression levels associated to 3 important values, weak expression of TCF-1, weak expression of LEF-1 and strong expression of LEF-1. Analysis of variances performed on the total sample also indicates significant differences in the values of TCF-1 weak (F=2.804 ; p=0.045), LEF-1 strong (F=5.498 ; p=0.002) and LEF-1 weak (F=4.255 ; p= 0.008) with regard to malignancy grade. The F–ratios for two variables (LEF-1 strong and LEF-1 weak) indicate that differences between astrocytomas and glioblastomas are statistically significant (P<0.01). Discriminant function analysis further showed that just one variable –the strong expression of LEF-1, emerged to discriminate between astrocytomas and glioblastomas. This suggests that LEF-1 may serve as potential diagnostic marker distinguishing glioblastoma from astrocytoma group. Based on our results we can conclude that astrocytic brain tumors are characterized by elevated levels of expression of both TCF-1 and LEF-1 transcription factors involved in the wnt signaling.

astrocytic brain tumors; glioblastoma; transcription factors TCF-1; LEF-1; wnt signaling

nije evidentirano