Suppression of human colorectal carcinoma cell growth by wild-type p53

Article Abstract:

Many tumor cells, especially those from malignancies of the rectum and colon, contain an abnormal gene on chromosome 17. This gene, called p53, is often either completely missing or is mutated in such a way that the gene's protein product is not manufactured. To evaluate the importance of p53 in tumor replication, normal (wild-type) or mutant genes were transfected into two cancer tumor cell lines (SW480 and SW837). This involves the insertion of genetic material that includes p53 into the tumor cells (transfection), and then observing the tumor's growth and other characteristics. Results showed that the wild-type p53 gene inhibited the growth of both cell lines such that five- to ten-fold fewer colonies (aggregations of cells) formed. However, some colonies did form, indicating that growth suppression was not total. When the cells from these colonies were analyzed, it was found that they expressed a mutant form of mRNA, and that the p53 gene itself was either deleted or rearranged, or both. Additional tests with another colorectal cancer cell line showed that wild-type gene expression (p53 protein) dramatically inhibited DNA synthesis, whereas mutated or absent p53 protein had no effect on the cells' DNA synthesis. WIld-type p53 was present in cells from a benign colon tumor, and no effects were observed on those cells when transfects were introduced. Thus, it appeared that expression of the wild-type p53 gene is associated with a lack of tumor cell proliferation. The effect is specific, both with respect to the mutations that occur and to the cell type whose growth is inhibited. The inhibitory effect may be especially potent for cells that are at malignant, rather than premalignant, stages of tumor progression. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Growth, Tumors

---

Identification of a chromosome 18q gene that is altered in colorectal cancers

Article Abstract:

The gene is the basic unit of heredity and occurs in pairs called alleles in the chromosomes, thread-like structures in the nucleus of the cell. Cancer research is currently focused on the role of oncogenes and tumor suppressor genes in the pathogenesis of various types of cancer. Oncogenes are genes that can induce a cell to become malignant, whereas tumor suppressor genes serve to prevent cells from transforming into cancerous cells. The most intensively studied human cancer is colorectal cancer because each step in the development of this cancer can be easily identified. Genetic studies have shown that the development of colorectal cancer involves the activation of the Ki-ras oncogene in 40 to 50 percent of the cases, and also the loss of genetic information, most likely tumor suppressor genes, from chromosome five in 35 percent of the cases, chromosome 17 in 70 percent of the cases and chromosome 18 in 70 percent of the cases. In this study, the deoxyribonucleic acid (DNA) segment that carries the genetic information lost on chromosome 18, was isolated and characterized. It was shown to carry the genetic information for what was designated the deleted in colorectal cancer (DCC) gene. The DCC gene codes for a protein similar in structure to nerve cell adhesion molecules and other cell surface proteins, and is reduced or absent in most colorectal cancers. The findings show that the DCC gene may play a role in the pathogenesis of colorectal cancer, perhaps through the alteration of the normal cell interactions involved in growth.

Research, Suppression, Genetic, Suppressor mutation (Molecular genetics), Chromosome deletion, Human chromosome abnormalities

---

Identification of p53 gene mutations in bladder cancers and urine samples

Article Abstract:

The genetic basis for bladder cancer (carcinoma), a disease that strikes approximately 18 people per 100,000 and is particularly prevalent among people in their 70s, was investigated by analyzing biopsy specimens from 18 patients with invasive bladder cancer. Because of the type of chromosomal aberrations observed in bladder cancer, a mutation in a gene that normally suppresses tumor growth (a suppressor gene), p53, was suspected. Using techniques of DNA amplification and analysis, bladder cells were evaluated for p53 mutations. These were detected in 11 of the 18 specimens (61 percent). The nature of the mutations is described. Examination of urine specimens from three of the patients revealed that the same mutations present in the tumor were also present in cells shed in the urine. The mutations were detected in between one and seven percent of shed cells. The results support the view that bladder cancer is associated with a defect in tumor-suppressor genes. The clinical applications of these very sensitive tests could include screening of people at high risk for bladder cancer (perhaps because of occupational exposure), or who have been treated for invasive bladder cancer. A brief review is presented of other mutations implicated in various forms of cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Methods, Diagnosis, Genetic screening, Genetic testing, Tumor suppressor genes, Bladder cancer

Similar abstracts:

• Abstracts: Measurement and prediction of the residual stress field generated by side-punching. Creep relaxation of residual stresses around cold expanded holes
• Abstracts: Cystic fibrosis corrected in lab. CF screening delayed for awhile, perhaps forever. To test or not to test?

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.