Class III β-Tubulin and γ-Tubulin are Co-expressed and Form Complexes in Human Glioblastoma Cells

Abstract

We have previously shown that the neuronal-associated class III beta-tubulin isotype and the centrosome-associated gamma-tubulin are aberrantly expressed in astrocytic gliomas (Cell Motil Cytoskeleton 2003, 55:77-96; J Neuropathol Exp Neurol 2006, 65:455-467). Here we determined the expression, distribution and interaction of betaIII-tubulin and gamma-tubulin in diffuse-type astrocytic gliomas (grades II-IV) (n = 17) and the human glioblastoma cell line T98G. By immunohistochemistry and immunofluorescence microscopy, betaIII-tubulin and gamma-tubulin were co-distributed in anaplastic astrocytomas and glioblastomas and to a lesser extent, in low-grade diffuse astrocytomas (P < 0.05). In T98G glioblastoma cells betaIII-tubulin was associated with microtubules whereas gamma-tubulin exhibited striking diffuse cytoplasmic staining in addition to its expectant centrosome-associated pericentriolar distribution. Treatment with different anti-microtubule drugs revealed that betaIII-tubulin was not associated with insoluble gamma-tubulin aggregates. On the other hand, immunoprecipitation experiments unveiled that both tubulins formed complexes in soluble cytoplasmic pools, where substantial amounts of these proteins were located. We suggest that aberrant expression and interactions of betaIII-tubulin and gamma-tubulin may be linked to malignant changes in glial cells.

Class III β-Tubulin Isotype Predicts Response in Advanced Breast Cancer Patients Randomly Treated Either with Single-Agent Doxorubicin or Docetaxel

“…Similar observations have been made in other types of tumors including ovarian cancer (17) and carcinomas of unknown origin (37). h-Tubulin III has also been found to be expressed in pancreatic adenocarcinoma and glioblastoma (38,39). Of interest, inhibition of class III tubulin has been shown to sensitize tumor cells to microtubule-binding agents (40).…”

Transcriptional and post-transcriptional regulation of βIII-tubulin protein expression in relation with cell cycle-dependent regulation of tumor cells

“…In glioblastoma cells, TUBB3 forms complexes with γ-tubulin (32), which is important for the nucleation and polar orientation of microtubules (12). Furthermore, TUBB3 expression has been demonstrated by immunohistochemistry in the large intestine, fibroblasts and keratinocytes under physiological conditions (9,10).…”

Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III β‐tubulin

“…In the former, such as cerebellar medulloblastomas, retinoblastomas, central and peripheral (sympathoadrenal) neuroblastomas and pheochromocytomas, the expression of bIII-tubulin in tumor cells is constitutive, associated with morphological changes of neuronal differentiation, such as elaboration of neuritc cell processes (neuritogenesis) and decreased cell proliferation (Katsetos et al, 2003a,b,c). In contrast, the expression of bIII-tubulin in non-neuronal tumors, such as common epithelial tumors of the lung, including small cell-and non-small cell lung carcinomas (NSCLC) (Katsetos et al, 2000;Dumontet et al, 2005;Sève et al, 2005aSève et al, ,b, 2007a, in adenocarcinomas of the ovary (Ferrandina et al, 2006;Ohishi et al, 2007), breast (Bernard-Marty et al, 2002;Hasegawa et al, 2003;Paradiso et al, 2005;Tommasi et al, 2007), stomach (Urano et al, 2006) and prostate, as well as in gliomas of the CNS (Katsetos et al, 2001(Katsetos et al, , 2002(Katsetos et al, , 2003b(Katsetos et al, , 2007, is associated with a trend towards an higher histological grade of malignancy and poor prognosis.…”

“…It is variably present in all glioma types and grades but when significantly increased, it tends to be associated with a higher histologic tumor grade (Katsetos et al, 2001(Katsetos et al, , 2002(Katsetos et al, , 2003aMao et al, 2007). The latter is exemplified in GBM, the most common and deadliest form of primary brain cancer in adults (Katsetos et al, 2001(Katsetos et al, , 2007.…”

“…During the past decade, we have demonstrated that GBMs exhibit significant changes in their microtubule cytoskeleton, including aberrant expression of the class III b-tubulin isotype (bIII-tubulin) and g-tubulin, which are associated with the emergence of highly malignant (anaplastic) tumor phenotypes (Katsetos et al, 2001(Katsetos et al, , 2002(Katsetos et al, , 2003a(Katsetos et al, ,b, 2006(Katsetos et al, , 2007.…”