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Expression of genes and differentiation markers in human glioblastoma cell lines

Gillaspy, Glenda E.

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1991, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
Glioblastomas are highly malignant tumors found in the central nervous system. To define some of their molecular driving forces, transcription rates of oncogenes and growth factors were examined in seven human glioblastoma cell lines and in three normal human glial cell populations. The following genes were over-expressed: PDGF-B in 4/7, EGF-R in 1/7, NEU in 1/7, IGF-2 in 1/7, ROS in 2/7, C-MYC in 2/7, and FOS in 1/7 glioblastomas. PDGF-R was under-expressed in 4/7. This suggests that these genes may be involved in the progression of normal glial cells to the tumor state. No one gene was over-expressed in all glioblastoma cell lines, thus, each had a unique pattern of over-expression. Developmental states of these same cell lines was investigated using antibodies which distinguish glial cell types in the rat optic nerve. The glial origin of each cell line was ascertained using GFAP and 7B11 antibodies. Three cell lines expressed an antigenic phenotype and morphology similar to rat O-2A progenitor cells (A2B5 and HNK-1-positive; GFAP and Gal-C-negative). Two of these cell lines could be forced to undergo differentiation in response to cAMP resulting in type-2 astrocyte-like cells (GFAP-positive) in one case, and in the other case, oligodendrocyte-li ke cells (Gal-C-positive). Three other glioblastoma cell lines appeared to be related to cells from the O-2A lineage, but were heterogeneous and did not undergo identifiable differentiation events following cAMP treatment. One glioblastoma cell line and the normal population were similar to type-1 astrocytes in antigenic phenotype (A2B5 and HNK-1-negative, GFAP-positive) and in morphology. The effect of this in vitro differentiation by cAMP was examined. Morphological alterations were inhibited by serum, and reversible when cAMP was removed. Growth inhibition and increases in glutamine synthetase enzyme activity resulted in 3/4 glioblastoma cell lines treated with cAMP. An overall decrease in the transcription rate of PDGF-B, ROS and IGF-2 resulted in one glioblastoma cell line differentiated with cAMP. PDGF-B mRNA levels were also decreased in this cell line in response to cAMP, but not in another glioblastoma cell line which did not differentiate in the presence of cAMP.
David Goldthwait (Advisor)
179 p.

Recommended Citations

Citations

  • Gillaspy, G. E. (1991). Expression of genes and differentiation markers in human glioblastoma cell lines [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1055265679

    APA Style (7th edition)

  • Gillaspy, Glenda. Expression of genes and differentiation markers in human glioblastoma cell lines. 1991. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1055265679.

    MLA Style (8th edition)

  • Gillaspy, Glenda. "Expression of genes and differentiation markers in human glioblastoma cell lines." Doctoral dissertation, Case Western Reserve University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1055265679

    Chicago Manual of Style (17th edition)