Expression of BAG-4, Bcl-2, and Hsp70 are related to tumor aggressiveness, according to Clinical Cancer Research paper.



An international scientific team found that the elevated levels of certain proteins  typically associated with keeping cancer cells alive may actually correspond with improved patient survival in ovarian cancer.


The investigators examined the protein expression patterns in 28 tumor samples collected from women treated at the NCI for stage III or IV ovarian cancer and 170 tissue samples archived at the Gynecological Oncology Group tissue bank.


The team found that elevated expression of BAG-4, an apoptosis inhibiting protein, localized outside the nucleus was strongly and positively associated with long-term patient survival. This included both overall and progression-free survival in newly diagnosed patients who were treated with chemotherapy that included a platinum-based drug.


The scientists also discovered that the cytoplasmic level of Bcl-2, another antiapoptotic protein that binds to BAG-4, was inversely related to tumor grade and stage at diagnosis. The opposite is true for other cancers; for instance, a higher Bcl-2 level in lymphomas correlates with cancer aggressiveness, according to the NCI.


A correlation between increased nuclear accumulation of the protein Hsp70, which also binds to BAG-4; a lower cytoplasmic level of Bcl-2; and higher tumor grade at diagnosis was also identified, which suggests that the baseline Hsp70 level could also be tied to a tumor’s aggressiveness at diagnosis, according to the researchers.


The study was conducted by the NCI and investigators at the Rikshospitalet-Radiumhospitalet Medical Centre. The findings are published in the November 15 issue of Clinical Cancer Research.








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