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Transcription and cancer
1Transcriptional Control Laboratory, Marie Curie Cancer Research, Oxted, Surrey, UK.
Abstract:
The normal growth, development and function of an organism requires precise and co-ordinated control of gene expression. A major part of this control is exerted by regulating messenger RNA (mRNA) production and involves complex interactions between an array of transcriptionally active proteins and specific regulatory DNA sequences. The combination of such proteins and DNA sequences is specific for given gene or group of genes in a particular cell type and the proteins regulating the same gene may vary between cell types. In addition the expression or activity of these regulatory proteins may be modified depending on the state of differentiation of a cell or in response to an external stimulus. Thus, the differentiation of embryonic cells into diverse tissues is achieved and the mature structure and function of the organism is maintained. This review focusses on the role of perturbations of these transcriptional controls in neoplasia. Deregulation of transcription may result in the failure to express genes responsible for cellular differentiation, or alternatively, in the transcription of genes involved in cell division, through the inappropriate expression or activation of positively acting transcription factors and nuclear oncogenes. Whether the biochemical abnormalities that lead to the disordered growth and differentiation of a malignant tumour affect cell surface receptors, membrane or cytoplasmic signalling proteins or nuclear transcription factors, the end result is the inappropriate expression of some genes and failure to express others. Current research is starting to elucidate which of the elements of this complicated system are important in neoplasia.
Insights
Gene expression control is vital for normal development. Deregulation of these controls, particularly transcription, is implicated in cancer development and progression.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Normal organism growth and function depend on precise gene expression control.
- Messenger RNA (mRNA) production is regulated by interactions between transcription factors and DNA sequences.
- Regulatory protein activity can be modulated by cell differentiation and external stimuli.
Purpose of the Study:
- To review the role of transcriptional control perturbations in neoplasia (cancer).
- To explore how disrupted gene expression contributes to disordered cell growth and differentiation in tumors.
Main Methods:
- Review of existing literature on transcriptional regulation and cancer.
- Analysis of mechanisms underlying gene expression deregulation in neoplastic cells.
Main Results:
- Perturbations in transcriptional control can lead to failed expression of differentiation genes or inappropriate expression of cell division genes.
- Both transcription factors and oncogenes play critical roles in driving neoplastic growth.
- Abnormalities at various cellular levels (receptors, signaling proteins, transcription factors) converge on altered gene expression patterns.
Conclusions:
- Disordered gene expression is a hallmark of cancer, resulting from failures or inappropriate activation of transcriptional regulatory pathways.
- Understanding the specific elements of transcriptional control involved in neoplasia is a key area for current research.