H-ras and Nm23-H1 gene expression and proteolytic activity in squamous cell carcinoma of the uterine cervix.

BACKGROUND: The invasive and metastatic potential of malignant cells results from complex interactions of numerous factors not yet fully understood. Genomic alterations such as ras overexpression and nm23-H1 inhibition have been found to be frequently associated with increased invasiveness in various cancers. On the other hand, secretion of different proteinases are necessary for malignant cells to traverse a network of matrix macromolecules, but the relationship between the genomic alterations and the proteolytic phenotype is still unclear. Our aim was to investigate whether the appearance of the proteolytic phenotype had any correlation with the expression of H-ras and nm23-H1 genes in carcinoma of the uterine cervix. METHODS: Twenty-five samples from patients with carcinoma of the uterine cervix at different clinical stages were studied. Cathepsin B1, plasminogen activator, and collagenase activity were assessed in tissue cytosols using specific synthetic oligopeptides as substrates. The expression of H-ras and nm23-H1 was investigated by means of immunohistochemistry and in situ hybridization. RESULTS: Our results showed that cathepsin B1 was the most consistently elevated proteinase, demonstrating a linear correlation with clinical staging. H-ras expression was found elevated in 40% of the cases. Nm23-H1 protein immunoreactivity was positive in 40% of the cases. No correlation was found among H-ras, cathepsin B1 activity, and survival rate. Among cases with high cysteine proteinase activity, a different clinical behavior depending on the expression of Nm23-H1 was observed. The cases with Nm23-H1 protein had a markedly better survival rate than those lacking this protein. In contrast, the absence of Nm23-H1 in association with high cathepsin B1 activity was a clear indicator of a poor prognosis. CONCLUSIONS: These findings suggest a complex interaction between the proteolytic phenotype and the expression of H-ras and nm23-H1 genes in carcinoma of the cervix that influences the clinical behavior of the tumor.

[MYC protein and proteins antigenically related with MYC in acute lymphoblastic leukemia]. / Estudio de la proteína MYC y de proteínas antigénicamente relacionadas a MYC en leucemia aguda linfoblástica (LAL).

The gross structure and the expression of the c-myc oncogene were analyzed in primary cells from 15 acute lymphoblastic leukemia patients. Southern blot analysis was used to detect possible alterations in the structure of this gene. Alterations (rearrangement and/or amplification) were observed in seven of the 15 samples studied. When the expression of MYC protein was evaluated by Western blot analysis, we found no correlation between c-myc gene alterations and p67 c-myc, which was expressed in the 15 samples studied. The analysis of expression also revealed various MYC-related proteins (115, 110 and 60 kD). These proteins were expressed at variable levels in all leukemic cells, other transformed cells, and in normal peripheral blood lymphocytes (PBL) induced to proliferate with interleukin 2. We detected the 110 kD and 40 kD MYC-related proteins in fresh normal PBL and in samples from patients in complete remission. These studies indicate that the c-myc alterations and protein expression are unrelated to percentage of leukemic blasts, cell morphology or immunophenotype. Our work shows that the expression of MYC-related proteins from 115, 60 and 40 kD is associated with mechanisms of cell activation, and perhaps these proteins may play a role in cellular proliferation-transformation.