[Heat shock proteins and malignancies of the female genital tract].

Heat shock proteins (Hsp) are cytoplasmic proteins that act as molecular chaperones for protein molecules in various intra-cellular processes. They play an important role in protein-protein interactions, including folding and conformation, and prevention of inappropriate protein aggregation. They are called "heat shock proteins" since they were first discovered in cells exposed to high temperatures. However, their synthesis is also accentuated under other stress conditions, such as exposure of the cell to inflammation, infection, ischemia, toxins, cytotoxic drugs and malignant transformation. Hsp have been classified into families according to their molecular weight. In ovarian carcinoma, over-expression of Hsp27 was associated with increased resistance to chemotherapy and a worse prognosis. In endometrial carcinoma, over-expression of Hsp70 was associated with poorly differentiated tumors and a worse prognosis, whereas over-expression of Hsp27 and Hsp90 were associated with well-differentiated tumors and better prognosis. The association between increasing expression of Hsp90 and better differentiation and prognosis seems to reflect high levels of sex steroid receptors in well-differentiated endometrial carcinomas. In cervical carcinoma, the presence of Hsp70 was associated with a worse outcome. Since Hsp are highly antigenic, their property to bind with tumor proteins and proteins produced by viruses may be used for the development of vaccines against cancers and viral diseases. It is speculated that examination of the lower genital tract secretions for IgA antibodies against Hsp will contribute to early detection of malignancies. Since Hsp may affect the growth of the tumor and its response to chemotherapy, it is speculated that using drugs that inhibit Hsp in combination with conventional chemotherapy may contribute to the improvement of the treatment results.

Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent.

Taxol is used in chemotherapy regimens against breast and ovarian cancer. Treatment of tumor model cell lines with taxol induces apoptosis, but exact mechanism is not sufficiently understood. Our results demonstrate that in response to taxol, various cell types differentially utilize distinct apoptotic pathways. Using MCF7 breast carcinoma cells transfected with caspase-3 gene, we showed that taxol-induced apoptosis occurred in the absence of caspase-3 and caspase-9 activation. Similar results were obtained with ovarian SKOV3 carcinoma cells, expressing high level of endogenous caspase-3. In contrast, staurosporine-induced apoptosis in these cells was accompanied by proteolytic cleavage of pro-caspase-3 and induction of caspase-3 enzymatic activity. The effect of taxol appears to be cell type-specific, since taxol-induced apoptosis in leukemia U937 cells involved caspase-3 activation step. We conclude that a unique caspase-3 and caspase-9 independent pathway is elicited by taxol to induce apoptosis in human ovarian and breast cancinoma cells.