期刊
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
卷 145, 期 9, 页码 2241-2250出版社
SPRINGER
DOI: 10.1007/s00432-019-02981-5
关键词
Melanoma; TRIM16; Keratinocyte; Carcinogenesis; Migration; Metastasis
类别
资金
- National Health and Medical Research Council (NHMRC), Australia [APP1016699]
- Cancer Institute NSW [10/TPG/1-13]
- Cancer Council NSW [PG-11-06]
Purpose The tripartite motif (TRIM)16 acts as a tumour suppressor in both squamous cell carcinoma (SCC) and melanoma. TRIM16 is known to be secreted by keratinocytes, but no studies have been reported yet to assess the relationship between TRIM16 keratinocyte expression and melanoma development. Methods To study the role of TRIM16 in skin cancer development, we developed a keratinocyte TRIM16-specific knockout mouse model, and used the classical two-stage skin carcinogenesis challenge method, to assess the loss of keratinocyte TRIM16 on both papilloma, SCC and melanoma development in the skin after topical carcinogen treatment. Results Heterozygous, but not homozygous, TRIM16 knockout mice exhibited an accelerated development of skin papillomas and melanomas, larger melanoma lesions and an increased potential for lymph node metastasis. Conclusion This study provides the first evidence that keratinocyte loss of the putative melanoma tumour suppressor protein, TRIM16, enhances melanomagenesis. Our data also suggest that TRIM16 expression in keratinocytes is involved in cross talk between keratinocytes and melanocytes, and has a role in melanoma tumorigenesis.
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