Involvement of the RAR{beta}1 and dlk genes in small cell lung carcinogenesis and in human development
- Institut du Cancer de Montreal, Quebec (Canada); and others
Lung cancer is the most lethal malignant disease in western societies. It encompasses four major histological types: squamous carcinoma, adenocarcinoma, and large cell carcinoma (known together as non-small-cell lung cancers) and a fourth type which is small cell carcinoma. This last histological class is a particularly aggressive malignant disease; it is characterized by an early development of metastasis so that upon time of diagnosis these are already widespread throughout the body. Our group is interested in defining and understanding the role of the retinoic acid receptor {beta}(RAR{beta}) gene in human lung cancer. This gene encodes nuclear transcription factors which are part of the thyroid and steroid hormone receptor superfamily. Four isoforms are known in mouse, which are generated by alternative splicing from two promoters, P{sub 1} (isoforms {beta}1 and {beta}3) and P{sub 2} (isoforms {beta}2 and {beta}4). In human only the isoforms {beta}2 (a tumor suppressor gene) and {beta}4 were known until recently when our group cloned the sequences encoding the 5{prime} end of the mRNA for RAR{beta}1. Expression studies have shown that this isoform is expressed during development in almost all tissues tested and that it is also expressed in a particular subset of human small cell carcinoma lines. It is not expressed in any adult tissue examined so far. Recently, Laborda et al. have cloned a human gene (dlk for delta-like) similar to the drosophila neurogenic gene Delta. We have found striking similarities in the expression pattern of dlk and RAR{beta}1 since the two genes are coexpressed in all fetal tissues examined and are also coexpressed in virtually identical subsets of SCLC lines. These results have implications for human embryogenesis and tumorigenesis.
- OSTI ID:
- 133588
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0317
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
A third human retinoic acid receptor, hRAR-. gamma
An EGF receptor inhibitor induces RAR-{beta} expression in breast and ovarian cancer cells