Abstract
BackgroundAntimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues.MethodsTo determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of Ī²-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues.ResultsĪ²-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant Ī²-tubulin isotypes in these tissues were Ī²-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5ā30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels.ConclusionThese results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40ā75% Ī²-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs.
Highlights
Common agents currently used in treating metastatic breast cancer are the antimitotics paclitaxel and docetaxel [1,2]
Tubulin isotypes in breast tissues by immunohistochemistry A total of 20 anonymous paired normal and tumor tissue samples were obtained from CHTN (Table 1)
We found no correlations between tubulin isotype levels and any of the variables given in the pathology reports
Summary
Common agents currently used in treating metastatic breast cancer are the antimitotics paclitaxel and docetaxel [1,2] These drugs bind to Ī²-tubulin, a major protein in mitotic spindles, and halt cell division at metaphase. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have