Class III β‐tubulin in human development and cancer

Abstract

The differential cellular expression of class III ␤-tubulin isotype (␤III) is reviewed in the context of human embryological development and neoplasia. As compared to somatic organs and tissues, ␤III is abundant in the central and peripheral nervous systems (CNS and PNS) where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar and sympathoadrenal neurogenesis, the distribution of ␤III is neuron-associated, exhibiting distinct temporospatial gradients according to the regional neuroepithelia of origin. However, transient expression of this protein is also present in the subventricular zones of the CNS comprising putative neuronal-and/or glial precursor cells, as well as in Kulchitsky neuroendocrine cells of the fetal respiratory epithelium. This temporally restricted, potentially non-neuronal expression may have implications in the identification of presumptive neurons derived from embryonic stem cells. In adult tissues, the distribution of ␤III is almost exclusively neuron-specific. Altered patterns of expression are noted in cancer. In "embryonal"-and "adult-type" neuronal tumors of the CNS and PNS, ␤III is associated with neuronal differen- Abbreviations: bHLH, basic helix-loop-helix; ␤III, class III ␤-tubulin isotype, CNE , central nervous system enhancer; CNS, central nervous system; EGL, external granule layer; MAP, microtubule-associated protein; NCAM, neural cell adhesion molecule; OPC, oligodendrocyte precursor cell; PCNA, proliferating cell nuclear antigen; PNS, peripheral nervous system; pRb, retinoblastoma tumor suppressor protein; PSA, polysialated; SVZ, subventricular zone; WHO, World Health Organization. tiation and decreased cell proliferation. In contrast, the presence of ␤III in gliomas and lung cancer is associated with an ascending histological grade of malignancy. Thus, ␤III expression in neuronal tumors is differentiation-dependent, while in non-neuronal tumors it is aberrant and/or represents "dedifferentiation" associated with the acquisition of progenitor-like phenotypic properties. Increased expression in various epithelial cancer cell lines is associated with chemoresistance to taxanes. Because ␤III is present in subpopulations of neoplastic, but not in normal differentiated glial or somatic epithelial cells, the elucidation of mechanisms responsible for the altered expression of this isotype may provide insights into the role of the microtubule cytoskeleton in tumorigenesis and tumor progression. Cell Motil. Cytoskeleton 55: 77-96, 2003.

Early Differentiating Mouse Astroglial Progenitors Share Common Protein Signatures with GL261 Glioma Cells

“…Mature astrocytic markers, such as GFAP, are also described to be expressed in glioma cells [53][54][55] , although Jan et al [51] showed that the malignant progression to a higher degree of invasiveness is associated with an increase in vimentin expression and a progressive loss of GFAP. Besides the expression of immature and astrocytic cell markers, gliomas also express neuronal proteins such as β-III-tubulin [56,57] and MAP2 [58] , both indicators of a high-grade astrocytoma [58] . Similarly, the expression of progenitor and mature oligodendrocytes markers are found in gliomas/astrocytomas [59,60] , although MBP is minimally expressed in GBM [59] .…”

Flip channel: A microfluidic device for uniform-sized embryoid body formation and differentiation

“…29,30 The cells are fixed in 4% paraformaldehyde (158127, Sigma-Aldrich) in D-PBS (Gibco 14190, Invitrogen) for 30 min, and then permeablized/blocked in fresh permeable-blocking solution composed of 5% normal donkey serum (017-000-001, Jackson ImmunoResearch, West Grove, PA), 0.3% Triton X-100 (T9284, Sigma-Aldrich) in 1X D-PBS for 2 h at room temperature. Then, cells are incubated with mouse anti-bIII-tubulin (1:500) antibody (Chemicon MAB1637, Millipore) for overnight at 4 C, washed three times, and incubated with Cy3-labeled donkey anti-mouse IgG (1:500) (Chemicon AP192C, Millipore) for 2 h in the dark.…”

Aberrant expression of class III β-tubulin in basal cell carcinoma of the skin

“…Tubulin consists of · and ß subunits. In mammals, six ß-tubulin isotypes have been identified and the complex variable patterns of their expression denote cellular and functional specificity and diversity (8).…”

“…Class III ß-tubulin (ß III) is a neuron-associated isotype that is considered to be one of the earliest neuron-associated cytoskeletal markers and is thought to play an important functional role in neuronal morphogenesis (8). ß III expression is observed throughout the lifetime from early development in the central and peripheral nervous systems and in some nerve tumors, such as high-grade gliomas (9), oligodendrogliomas (10), medulloblastomas (11), retinoblastomas (12), and pheochromocytomas (13).…”