The betaII isotype of tubulin is present in the cell nuclei of a variety of cancers

Abstract

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 betaII isotype of tubulin in their nuclei in the form of an alphabetaII 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 betaII 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 betaII-tubulin occurs in the nuclei of actual cancers as well as in cancer cell lines, we used the immunoperoxidase method to look for nuclear betaII in a variety of tumors excised from 201 patients. We found that 75% of these tumors contain betaII in their nuclei. Distribution of nuclear betaII 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 betaII. Nuclear betaII was particularly marked in tumors of epithelial origin, of which 83% showed nuclear betaII, in contrast to 54% in tumors of non-epithelial origin. In many cases, betaII staining occurred very strongly in the nuclei and not in the cytoplasm; in other cases, betaII was present in both. In many cases, particularly metastases, otherwise normal cells adjacent to the tumor also showed nuclear betaII, suggesting that cancer cells may influence nearby cells to synthesize betaII and localize it to their nuclei. Our results have implications for the diagnosis, biology, and chemotherapy of cancer.