The β_II Isotype of Tubulin Is Present in the Cell Nuclei of a Variety of Cancers

Tubulin, the subunit protein of microtubules, has generally been thought to be exclusively a cytoplasmic protein in higher eukaryotes. We have previously shown that cultured rat kidney mesangial cells contain the β_II isotype of tubulin in their nuclei in the form of an αβ_II dimer [Walss et al., 1999: Cell Motil. Cytoskeleton 42:274-284, 1999]. More recently, we examined a variety of cancerous and non-cancerous cell lines and found β_II in the nuclei of all of the former and only a few of the latter (Walss-Bass et al., 2002: Cell Tissue Res. 308:215-223]. In order to determine if β_II-tubulin occurs in the nuclei of actual cancers as well as in cancer cell lines, we used the immunoperoxidase method to look for nuclear β_II in a variety of tumors excised from 201 patients. We found that 75% of these tumors contain β_II in their nuclei. Distribution of nuclear β _II was highly dependent on the type of cancer, with 100% of the colon and prostate cancers, but only 19% of the skin tumors, having nuclear β_II. Nuclear β_II was particularly marked in tumors of epithelial origin, of which 83% showed nuclear β_II, in contrast to 54% in tumors of non-epithelial origin. In many cases, β_II staining occurred very strongly in the nuclei and not in the cytoplasm; in other cases, β_II was present in both. In many cases, particularly metastases, otherwise normal cells adjacent to the tumor also showed nuclear β_II, suggesting that cancer cells may influence nearby cells to synthesize β_II and localize it to their nuclei. Our results have implications for the diagnosis, biology, and chemotherapy of cancer.