Chapter III. 1. Mutations in human breast cancer cells: Dominantly-acting oncogenes and tumor suppressor genes suggest strategies for targeted interference
✍ Scribed by Bernd Groner; Nancy E. Hynes
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- French
- Weight
- 745 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The etiology of breast cancer has been linked in the past to a number of "macroscopic" events which include the family history of cancer, benign breast disease, reproductive history, exposure to estrogens and diet. The disease itself has been analyzed at different stages and premalignant initiation and promotion have been proposed to precede malignant tumor growth, progression to metastasis and hormone independence of cell proliferation.
The consistent alterations of individual proto-oncogenes in breast cancer cells have given rise to the hope that individual disease parameters can be correlated with distinct cancer genotypes and that progress in diagnosis and therapy might be derived from the identification of altered proto-oncogenes, the elucidation of their function, and the interference with their activation . This concept is still in its early stages and the phase of data collection is not yet over. Distinct proto-oncogenes have been found to be amplified and over-expressed in breast cancer cells, others have been excluded. Tumor suppressor genes have been found to be inactivated and a number of genetic loci have been identified which are consistently mutated, but which are not yet correlated with a distinct gene or gene product. The discrepancy in the molecular resolution of the function of individual gene products presents a major obstacle for a comprehensive picture. Growth factors and their receptors have been extensively studied as far as their initial mode of action is concerned. The trail, however, is lost soon after the activation of the transmembrane receptors occurs, and a connection between cell-surface events, gene regulation and cellular phenotype will require many more years of study. Other oncogene products are even more elusive. In particular, the action of cytoplasmic and nuclear oncogenes is insufficiently understood. Even the extensively studied steroid receptor gene family only allows a glimpse into the transformation process. Although we understand the concept of inducible transcription factors in molecular detail, the cascade of events, i.e. the genes regulated by the estrogen or thyroid hormone receptors which are important for cell growth or arrest, are not known.
We will shortly introduce the known proto-oncogenes which play a role in breast cancer, summarize their properties and the evidence for their tumorigenic potential, and finally evaluate strategies which might become useful in therapy and which might precede the comprehensive understanding of oncogene functions.