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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Ryan, K. Tsuchiya, K. Swisshelm, K. Sager, R. |
Description | Author Affiliation: Swisshelm K ( Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.); |
Abstract | mac25, the subject of this report, was selected by the differential display of mRNA method in a search for genes overexpressed in senescent human mammary epithelial cells. mac25 had previously been cloned as a discrete gene, preferentially expressed in normal, leptomeningial cells compared with meningioma tumors. mac25 is another member of the insulin growth factor-binding protein (IGFBP) family. Insulin-like growth factors are potent mitogens for mammary epithelial cells, and the IGFBPs have been shown to modulate this mitogenic activity. We report here that mac25, unlike most IGFBPs, is down-regulated at the transcription level in mammary carcinoma cell lines, suggesting a tumor-suppressor role. The gene was mapped to chromosome 4q12. We found that mac25 accumulates in senescent cells and is up-regulated in normal, growing mammary epithelial cells by all-trans-retinoic acid or the synthetic retinoid fenretinide. These findings suggest that mac25 may be a downstream effector of retinoid chemoprevention in breast epithelial cells and that its tumor-suppressive role may involve a senescence pathway. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 10 |
Volume Number | 92 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 1995-06-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Breast Metabolism Carrier Proteins Biosynthesis Chromosomes, Human, Pair 4 Gene Expression Tretinoin Pharmacology Amino Acid Sequence Breast Neoplasms Cell Aging Cells, Cultured Chromosome Mapping Consensus Sequence DNA Replication Epithelial Cells Epithelium Drug Effects Fenretinide Insulin-Like Growth Factor Binding Proteins Kinetics Molecular Sequence Data RNA, Messenger Sequence Homology, Amino Acid Somatomedins Time Factors Comparative Study Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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