The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early melanomas Journal Article
| Authors: | Polsky, D.; Young, A. Z.; Busam, K. J.; Alani, R. M. |
| Article Title: | The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early melanomas |
| Abstract: | The helix-loop-helix transcription factor Idl coordinates cell growth and differentiation pathways within mammalian cells and has been implicated in regulating GI-S phase cell cycle transitions. Recently Idl has been shown to repress Ets- and E-protein-mediated transactivation of p16/Ink4a. Because the p16/Ink4a protein has been demonstrated to be inactivated in subsets of familial and sporadic melanomas, we sought to determine whether Idl regulation of p16/Ink4a expression might be involved in the development of this human tumor. Here we evaluate 21 melanocytic lesions at various stages of malignant progression from common melanocytic nevi to metastatic melanomas and examine these lesions for Idl and p16/Ink4a expression. We demonstrate that Idl expression correlates with loss of p16/Ink4a expression in melanoma in situ; However, more advanced stages of melanoma do not express Idl except within perivascular regions, despite overall decreased p16/Ink4a expression in these lesions. Microdissected lesions were evaluated for p16/Ink4a sequence, and invasive melanomas that did not express Idl were found to have sustained inactivating p16/Ink4a mutations. These data suggest a role for Idl in regulating p16/Ink4a expression in early melanomas and demonstrate that later genetic changes may provide for irreversible loss of p16 expression in advanced stages of this tumor. |
| Keywords: | senescence; keratinocytes; cutaneous melanoma; expression; tumor-suppressor gene; inactivation; loop-helix proteins; immortalization; id-1; cancer |
| Journal Title: | Cancer Research |
| Volume: | 61 |
| Issue: | 16 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2001-08-15 |
| Start Page: | 6008 |
| End Page: | 6011 |
| Language: | English |
| ACCESSION: | WOS:000170521100011 |
| PROVIDER: | wos |
| PUBMED: | 11507043 |
| Notes: | Article -- Source: Wos |
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