Class III β-tubulin in human development and cancer

Abstract

The differential cellular expression of class III β-tubulin isotype (βIII) is reviewed in the context of human embryological development and neoplasia. As compared to somatic organs and tissues, βIII 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 βIII 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 βIII 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, βIII is associated with neuronal differentiation and decreased cell proliferation. In contrast, the presence of βIII in gliomas and lung cancer is associated with an ascending histological grade of malignancy. Thus, βIII 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 βIII 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. © 2003 Wiley-Liss, Inc.