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High frequency of retinoic acid receptor beta abnormalities in human lung cancer
J F Gebert1, N Moghal, J V Frangioni
1Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts 02215.
Abstract:
One of the three human retinoic acid receptors, RAR-beta, maps to a region on the short arm of chromosome 3 frequently deleted in lung cancer. Because retinoic acid is required for normal epithelial cell growth and regulation, and loss of a retinoic acid receptor might be expected to contribute to oncogenesis, we examined RAR-beta RNA and DNA in normal lung, 33 lung cancer cell lines and nine primary lung tumors. Normally, RAR-beta is expressed as two transcripts, of sizes 3.1 kb and 2.8 kb, which are strongly induced by retinoic acid. At least 50% of the cell lines and 30% of the tumor samples show altered RAR-beta expression and/or inducibility, including examples of absence or specific loss of one of the RAR-beta transcripts. Abnormalities in the expression patterns of RAR-alpha and RAR-gamma also are found, but at a lower frequency than RAR-beta abnormalities. Southern analysis reveals alteration of the RAR-beta gene in three of the cell lines. Our data suggest that abnormalities in structure and expression of the RAR-beta gene may be involved in the pathogenesis of lung cancer.
Insights
Retinoic acid receptor beta (RAR-beta) gene abnormalities are common in lung cancer. Altered RAR-beta expression and DNA structure may contribute to lung cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Retinoic acid is crucial for epithelial cell growth and regulation.
- The RAR-beta gene is located on chromosome 3p, a region often deleted in lung cancer.
- Loss of RAR-beta function could potentially promote oncogenesis.
Purpose of the Study:
- To investigate RAR-beta RNA and DNA alterations in lung cancer.
- To determine the frequency of RAR-beta gene abnormalities in lung cancer cell lines and tumors.
- To assess the expression patterns of RAR-alpha and RAR-gamma in lung cancer.
Main Methods:
- Analysis of RAR-beta RNA and DNA in normal lung tissue, 33 lung cancer cell lines, and nine primary lung tumors.
- Examination of RAR-beta transcript sizes (3.1 kb and 2.8 kb) and retinoic acid inducibility.
- Southern blot analysis to detect alterations in the RAR-beta gene structure.
Main Results:
- Over 50% of lung cancer cell lines and 30% of tumor samples exhibited altered RAR-beta expression or inducibility.
- Specific instances of absent or reduced RAR-beta transcripts were observed.
- RAR-beta gene structure alterations were identified in three cell lines.
- Abnormalities in RAR-alpha and RAR-gamma expression were less frequent than RAR-beta alterations.
Conclusions:
- Aberrant RAR-beta gene structure and expression are implicated in lung cancer pathogenesis.
- These findings highlight the potential role of RAR-beta dysfunction in the development of lung cancer.
- Further research into RAR-beta's role in lung carcinogenesis is warranted.