Cytomegalovirus Gene Role May Differ in Brain Tumors
IE1 expression associated with proliferation in some glioma cells, arrested growth in others
WEDNESDAY, Feb. 6 (HealthDay News) -- A gene that's highly expressed after human cytomegalovirus (HCMV) infection, which has been found in over 90 percent of malignant gliomas, can differentially affect tumor cell growth, leading to proliferation or inhibition of glioblastoma cells, according to research published in the Feb. 1 issue of Cancer Research.
Charles S. Cobbs, M.D., of the California Pacific Medical Research Institute in San Francisco, and colleagues investigated the effects of HCMV immediate early-1 (IE1) protein in different cells, including U87, U118, LN229 and U251 glioblastoma cells and immortalized human astrocytes.
In the U87 and U118 cells, IE1 led to cellular proliferation by reducing the steady-state expression level of Rb and p53 family proteins, which are tumor suppressor proteins in gliomas. In these cells, IE1 also induced the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which is critical in gliomas. However, in LN229 and U251 and immortalized astrocytes, IE1 expression was associated with greater p53 protein expression, and arrested growth or lack of increased proliferation.
"Although we did not find classic transforming activity associated with IE1, sustained expression of IE1 along with multiple other HCMV gene products that can inhibit cell apoptotic pathways and promote neoplastic transformation could greatly affect the oncogenic phenotype of tumor cells expressing such HCMV gene products. Given the fact that we and others showed expression of IE1 in human glioblastomas in vivo, these findings may have relevance to the pathogenesis of this malignancy," the authors conclude.