Background: Angiogenesis is a key process in the development of a malignant tumor, enabling both growth of primary lesion and spread of metastases. Most potent stimulators of normal and pathological angiogenesis are proteins of the vascular endothelial growth factor (VEGF) family. Regulation of angiogenesis process is also mediated by neuropilin- 1 (NP-1), as coreceptor VEGFR-2. NP-1 plays a crucial role controlling both normal angiogenesis during embryonal development and pathological angiogenesis in malignant tumors. The aim of this paper was to assess NP-1 expression in ovarian cancer and to analyze correlations between NP-1 expression and selected clinical-pathological factors in a group of ovarian cancer patients. Material and method: Analyzed was the relative level of NP-1 in 168 surgical specimens collected during surgical procedures performed at the Department of Oncologic Gynecology of Medical University in Gdańsk. Tissue samples included: 32 healthy tissues, 42 benign tumors, 10 borderline tumors, 76 ovarian cancers, 8 metastatic tumors. Relative NP-1 level was assessed using Western blotting technology. Results: Overexpression of NP-1 was seen significantly more often in early clinical stages of ovarian cancer (p=0.01), in cancers other than serous (p=0.04) and in patients with peritoneal exudate (p=0.03). Log-rank test did not reveal any significant correlation between NP-1 expression and favorable response to chemotherapy, disease-free survival or total survival time. Conclusions. Elevated NP-1 level seen in initial clinical stages of ovarian cancer may indicate crucial role of neoangiogenesis in the early phase of tumor development.
Escherichia coli small heat shock proteins, IbpA/B, function as molecular chaperones and protect misfolded proteins against irreversible aggregation. IbpA/B are induced during overproduction of recombinant proteins and bind to inclusion bodies in E. coli cells. We investigated the effect of ΔibpA/B mutation on formation of inclusion bodies and biological activity of enzymes sequestered in the aggregates in E. coli cells. Using three different recombinant proteins: Cro-β-galactosidase, β-lactamase and rat rHtrA1 we demonstrated that deletion of the ibpA/B operon did not affect the level of produced inclusion bodies. However, in aggregates containing IbpA/B a higher enzymatic activity was detected than in the IbpA/B-deficient inclusion bodies. These results confirm that IbpA/B protect misfolded proteins from inactivation in vivo.
Serine proteases HtrA1 and HtrA2 are involved in cellular stress response and development of several diseases, including cancer. Our aim was to examine the involvement of the HtrA proteins in acute oxidative stress response induced in hamster kidney by estrogen treatment, and in nephrocarcinogenesis caused by prolonged estrogenization of male Syrian hamster. We used semi-quantitative RT-PCR to estimate the HtrA1 and HtrA2 mRNA levels in kidney tissues, and Western blotting to monitor the amount of the HtrA proteins. Within the first five hours following estrogen administration both HtrA1 mRNA and the protein levels were increased significantly. No changes in the expression of HtrA2 were observed. This indicates that HtrA1 may be involved in the response against oxidative stress induced by estrogen treatment in hamster kidney. During prolonged estrogenization, a significant reduction of the HtrA1 mRNA and protein levels was observed after 6 months of estradiol treatment, while the expression of HtrA2 was significantly elevated starting from the third month. This suggests an involvement of the HtrA proteins in estrogen-induced nephrocarcinogenesis in hamster. Using fluorescence in situ hybridization we localized the HtrA1 gene at the qb3-4 region of Syrian hamster chromosome 2, the region known to undergo a nonrandom deletion upon prolonged estrogenization. It is possible that the reduced level of HtrA1 expression is due to this chromosomal aberration. A full-length cDNA sequence of the hamster HtrA1 gene was obtained. It codes for a 50 kDa protein which has 98 and 96% identity with mouse and human counterparts, respectively.
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