Beta class II tubulin predominates in normal and tumor breast tissues.
BACKGROUND
Antimitotic 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.


METHODS
To 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 beta-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.


RESULTS
Beta-tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant beta-tubulin isotypes in these tissues were beta-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5-30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels.


CONCLUSIONS
These 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, 40-75% beta-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs.
Dozier
James H
JH
School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Hiser
Laree
L
Davis
Jennifer A
JA
Thomas
Nancy Stubbs
NS
Tucci
Michelle A
MA
Benghuzzi
Hamed A
HA
Frankfurter
Anthony
A
Correia
John J
JJ
Lobert
Sharon
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D001940:Breast / Q000737:chemistry*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014404:Tubulin / Q000096:biosynthesis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D014404:Tubulin