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Published on: November 2, 2013
H-ras and Nm23-H1 gene expression and proteolytic activity in squamous cell carcinoma of the uterine cervix
D Utrera-Barillas1, M Salcedo-Vargas, P Gariglio-Vidal
1Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), México, D.F., Mexico.
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.
Insights
Cervical cancer invasiveness involves complex gene and protein interactions. Nm23-H1 expression significantly impacts survival, especially when combined with high cathepsin B1 activity, indicating a poor prognosis without it.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant cell invasion and metastasis involve complex, not fully understood factors.
- Genomic alterations (e.g., ras overexpression, nm23-H1 inhibition) and proteolytic enzyme secretion are linked to cancer invasiveness.
- The relationship between genomic alterations and proteolytic phenotypes in cervical cancer remains unclear.
Purpose of the Study:
- To investigate the correlation between proteolytic phenotype and H-ras and nm23-H1 gene expression in cervical cancer.
- To understand the influence of these factors on tumor invasiveness and patient prognosis.
Main Methods:
- Studied 25 cervical cancer patient samples across different clinical stages.
- Assessed cathepsin B1, plasminogen activator, and collagenase activity using specific substrates.
- Investigated H-ras and nm23-H1 gene expression via immunohistochemistry and in situ hybridization.
Main Results:
- Cathepsin B1 was the most elevated proteinase, correlating linearly with clinical stage.
- H-ras and Nm23-H1 protein expression were found in 40% of cases.
- High cathepsin B1 activity with absent Nm23-H1 indicated a poor prognosis, while Nm23-H1 presence correlated with better survival.
Conclusions:
- A complex interplay exists between the proteolytic phenotype and H-ras/nm23-H1 gene expression in cervical carcinoma.
- These interactions significantly influence the tumor's clinical behavior and patient prognosis.
- Nm23-H1 expression is a critical factor in determining survival outcomes in conjunction with proteolytic activity.
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