| Abstract |
The expression levels of a total of 15 cell cycle regulatory proteins have
been determined in a panel of breast cancer and normal breast epithelial
cell lines, as well as in a number of breast tissue and normal breast
epithelial tissue samples. The results of these analyses indicate the
presence of a defect in the expression of cyclin D1, Rb and/or the cyclin
dependent kinase inhibitor protein, p16, in essentially all the breast
cancer cell lines and tissues studied. The degree of overexpression of
cyclin D1 is most closely reflected by changes in mRNA levels, although
gene amplification and in one case an increase in half-life of the protein
also contribute. Homozygous deletion of the p16 gene has been found to be
a frequent mechanism for the absence of this tumor suppressor protein in
breast cancer. Construction of replication incompetent adenovirus vectors
for high efficiency transfection of breast cancer cells with genes
encoding antisense cyclin D1 and sense p16 has been essentially completed.
Human breast cancer cell lines tumorigenic in nude mice have been
identified and will be transfected with these adenoviral vectors to
directly test and confirm the role of cyclin D1 and p16 expression in
breast cell tumorigenicity.
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