Cyclin E, a Potential Prognostic Marker in Breast Cancer.
Annual rept. 1 Oct 94-30 Sep 95,
HEALTH RESEARCH INC ALBANY NY
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We have shown severe quantitative and qualitative alterations in cyclin B protein expression independent of the S-phase fraction in human mammary epithelial cell lines as well as surgical material obtained from patients with various malignancies. In addition in breast cancer, the alterations in cyclin E expression become progressively worse with increasing stage and grade of the tumor suggesting its potential use as a new prognostic marker. We also analyzed the kinase activity associated with cyclin B in a number of asynchronous normal and tumor cell lines as well as synchronized population of these cells. These analyses revealed that cyclin B associated kinase activity is present at much higher levels in all tumor versus normal cell lines and that while in normal cells cyclin E activity is cell cycle regulated, in tumor cells it remains as an active complex throughout the cell cycle. To analyze cyclin B for possible alterations which could result in its constitutive expression, we reverse transcribed and polymerase chain reaction RT-PCR amplified cyclin E cDNA from a tumor line MDA-MB-157, cloned and sequenced the products and found two novel truncations in the cyclin B coding region. These truncations were found to be of general occurrence in most normal and tumor cell lines as well as normal adjacent and tumor tissue samples from breast cancer patients as detected in RT-PCR assays. However Western blot analysis indicated that the multiple isoforms of cyclin E protein were expressed only in the tumor tissue samples.
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