In: NEOPLASMA, vol. 54, no. 4
A. Hlobilková - J. Ehrmann - E. Sedláková - V. Krejci - P. Knizetova - M. Fiuraskova - M. Kala - O. Kalita - Z. Kolar
Detaily:
Rok, strany: 2007, 334 - 341
O článku:
The most frequent alterations found in astrocytomas are two major groups of signaling proteins: the cell cycle and the
growth factor-regulated signaling pathways. The aim of our study was to detect changes in expression of the following
proteins: the tumor suppressors PTEN, p53, and p21Waf1/Cip1, glial fibrillary acidic protein (GFAP, as a marker of astroglial
differentiation), the phosphorylated form of protein kinase B/Akt (PKB/Akt), which is downstream to the epidermal growth
factor receptor (EGFR), and MDM2, which degrades p53. Paraffin-embedded astrocytoma tissue samples from 89 patients
were divided into low grade (grade I-II; 42 samples) and high grade astrocytomas (grade III-IV; 47 samples). Mouse monoclonal
antibodies against GFAP, PTEN, PKB/Akt phosphorylated on serine 473, EGFR, p53, p21Waf1/Cip1 and MDM2 were used,
followed by standard indirect immunohistochemical method. EGFR protein was detected in 29 % of low grade and in 60 %
of high grade astrocytomas. The expression of phosphorylated PKB/Akt was found in roughly the same proportions: in 86%
of low grade and in 79% of high grade astrocytomas. PTEN was not found in most of astrocytomas, 64% of low grade and
74% of high grade tumors showed no PTEN staining. Overexpression of the mutated form of p53 or loss of p53 expression,
however, was found in about 63% in both groups of astrocytomas with no differences between them. GFAP expression was
decreased in tumor astrocytes compared to normal astrocytes and this decreased with grading. GFAP positive tumor cells
were detected in only 50% of low grade, and 32% of high grade astrocytomas. The level of MDM2 expression was similar
in both grades. Loss of p21Waf1/Cip1 expression was shown in 20% of low and in 45% of high grade tumors. In the subgroup
of high grade tumors with wild type p53, 86% showed p21Waf1/Cip1 expression, whereas in the subgroup of high grade tumors
with altered p53, only 35% displayed p21Waf1/Cip1. We conclude that EGFR expression increases with astrocytoma grading.
EGFR activation may subsequently lead to stimulation of the PKB/Akt survival pathway. PTEN defects may also participate
in aggressive tumor behaviour through activation of the PKB/Akt pathway. The alteration of p53 supports the finding that
the cell cycle regulation is also disrupted during development of astrocytomas. The changes in PTEN and p53 expression,
and activation of PKB/Akt are events in the early stages of astrocytomagenesis. EGFR is one of the factors, which drives the
progression of astrocytomas from low to high grade stage.
Key words: astrocytoma, PI3K/PKB/Akt pathway, cell cycle and immunohistochemistry
Ako citovať:
ISO 690:
Hlobilková, A., Ehrmann, J., Sedláková, E., Krejci, V., Knizetova, P., Fiuraskova, M., Kala, M., Kalita, O., Kolar, Z. 2007. Could changes in the regulation of the PI3K/PKB/Akt signaling
pathway and cell cycle be involved in astrocytic tumor pathogenesis
and progression?. In NEOPLASMA, vol. 54, no.4, pp. 334-341. 0028-2685.
APA:
Hlobilková, A., Ehrmann, J., Sedláková, E., Krejci, V., Knizetova, P., Fiuraskova, M., Kala, M., Kalita, O., Kolar, Z. (2007). Could changes in the regulation of the PI3K/PKB/Akt signaling
pathway and cell cycle be involved in astrocytic tumor pathogenesis
and progression?. NEOPLASMA, 54(4), 334-341. 0028-2685.