Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma

NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). There is abundant mRNA expression of NM23-H1, NM23-H2, or a read through transcript (NM23-LV) in the primary sites of hepatocellular carcinoma (HCC). Although the NM23-H1 protein is implicated as a metastasis suppressor, the role of NM23-H2 appears to be less understood. Thus, the aim of this study was to examine whether NM23-H2 is associated with hepatocarcinogenesis. The level of NM23-H2 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Its subcellular localization was confined to mainly the cytoplasm and to a lesser extent in the nucleus. Ectopic expression of NM23-H2 in NIH3T3 fibroblasts and HLK3 hepatocytes showed a transformed morphology, enhanced focus formation, and allowed anchorage-independent growth. Finally, NIH3T3 fibroblasts and HLK3 hepatocytes stably expressing NM23-H2 produced tumors in athymic mice and showed c-Myc over-expression. In addition, NF-kappaB and cyclin D1 expression were also increased by NM23-H2. Lentiviral delivery of NM23-H2 shRNA inhibited tumor growth of xenotransplanted tumors produced from HLK3 cells stably expressing NM23-H2. Collectively, these results indicate that NM23-H2 may be pro-oncogenic in hepatocarcinogenesis.

Study of angiogenesis, P53 and NM23 expression in colorectal carcinoma

Colorectal carcinoma [CRC] is not uncommon in Egypt. Sustained angiogenesis is characteristic of several pathological conditions including tumor growth. Many researches were conducted to investigate the role of P53 in colorectal carcinogenesis; also the role of NM23 in tumor progression and for metastasic potential is not so clear in CRC. In this research we are aiming to study the pattern and density of angiogenesis in colorectal carcinomas, in addition to other histopathological prognostic factors. Besides we are also aiming to study the expression of P53 and NM23 and the relation between these three factors [Angiogenesis, P53 and NM23] in different grades and stages of colorectal carcinomas. The study comprised 44 resection specimens of colorectal carcinomas collected from specimens of department of pathology, Faculty of Medicine, Tanta University Hospital and from same of the private laboratories. Each block was stained by hematoxylin and eosin [H and E], immunohistochemical stain for CD34, VEGF, P53 and NM23. Histopathological assessment of grading was done according to WHO classification and staged according to TNM classification. The present study includes 44 cases of colorectal adenocarcinoma 35 were male patients and 9 cases were females. The age range was 20 to 80 years. The patients were grouped into three groups as follows: Group [1]: CRC without nodal or distant metastasis, group [II]: CRC with nodal but no distant metastasis and group [III]: CRC with distant metastasis. Most of the tumors were conventional invasive adenocarcinomas, on studying angiogenesis we found that the relation of microvascular density [MVD] detected by CD34 was not significant with the tumor size. Besides there were a significant results between the microvascular density and metastatic history of the disease. There were significant results between VEGF expression and the studied variables. The study ol apoptosis using P53 reveals significant relation between it and the studied variables but not with the nodal or blood metastasis, there was an inverse relation between NM23 and both VEGF and P53, but the results was not significant with the tumor grade and size, so in the present study the relation between VEGF, P53 and NM23 was significant but each marker have its own variable result with the grade .size and the stage of the tumor. In the present study it can be concluded that MVD at vascular hot spots is a very important predictive factor in CRC in addition to VEGF .P53 over expression has an impact on the biological behavior of CRC being more expressed in biological aggressive tumors and it has a role in angiogenicStudy of Angiogenesis, P53 and NM23 Expression in Colorectal Carcinoma activity of the tumor. We also concluded that NM23 is an important metastatic suppressor gene in CRC. So NM23, P53, VEGF and MVD by CD34 all are important to predict the outcome of the disease and they can be used as a guide for treatment. MVD, microvascular density; VEGF, vascular endothelial growth factor; CRC, colorectal carcinoma