Shostak K. Gene expression changes in human glial tumors

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0402U003090

Applicant for

Specialization

  • 03.00.03 - Молекулярна біологія

22-10-2002

Specialized Academic Board

Д26.237.01

Essay

23 nucleotide sequences with altered expression in glial tumors have been identified by differential hybridization of arrayed human fetal brain and human postnatal brain cDNA libraries with total cDNAs probes of glioblastoma multiforme and normal brain. Revealed accumulation of heterodispersed RNAs containing Alu-repeats and polyadenylated mitochondrial and cytoplasmatic rRNAs. Increased expression of DNA-binding protein B (dbp B) gene was revealed in the astrocytomas of different malignancy grades. High-level activation of ZFM/SF1 gene was determined in anaplastic astrocytomas. The increased expression of Id-4 gene was found prevalently in the anaplastic astrocytomas and it may be involved in cell cycle abnormalities. Decrease of the expression of cullin-1 gene in astrocytic tumors may be connected to the cell cycle breakage in phase G1 to G0. Significant increase of HC gp-39 gene expression, found exclusively in high-grade astrocytomas, anaplastic astrocytoma and glioblastoma multiforme, is the evidence of important role of this gene in the progression of astrocytomas to more malignant phenotype. HC gp-39 may serve as molecular marker by the investigation of malignant progression of astrocytic gliomas or the distinguishing of glioblastoma multiforme between brain tumors. Decreased content and even complete absence of TSC-22 mRNA in human brain tumors, revealed by other authors inactivation of TSC-22 gene in benign and malignant human salivary gland tumors, transcription repressor activity of TSC-22, negative regulatory effect of TSC-22 on cell proliferation, all this strongly suggest the possible tumor suppressor role for TSC-22 gene. The polymorphism of gene expression in different samples of same malignancy grade reflects the heterogeneity of the pathways of the initiation and developments of astrocytic gliomas.

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