Record Details
Characterization of BRAF (V600E) Splice Variants in Metastatic and Drug-Resistant Melanoma
ScholarsArchive at Oregon State University
| Field | Value |
|---|---|
| Title | Characterization of BRAF (V600E) Splice Variants in Metastatic and Drug-Resistant Melanoma |
| Names |
Sawka, Erika M.
(creator) Indra, Arup (advisor) |
| Date Issued | 2015-05-28 (iso8601) |
| Note | Access restricted, at author's request, from June 8, 2015-Jun.8, 2017. |
| Abstract | The BRAF proto-oncogene is a member of the Raf protein family that encodes serine/threonine protein kinases, which activate the MEK/ERK signaling transduction pathway. The V600E mutation of BRAF, found in 70% of melanoma cases, causes an upregulation of MEK/ERK signaling which leads to many hallmarks of cancer, including apoptosis evasion, proliferation, angiogenesis, and metastasis. Protein isoforms resulting from alternative splicing found in BRAF V600E may influence its basal kinase activity in melanocytes and also contribute to drug resistance of melanoma tumors through Ras- independent enhanced dimerization. Two novel splice variants were identified and their relative expression was measured in human samples of non-cancerous melanocytes, BRAF V600E melanoma, and drug-resistant BRAF V600E melanoma. It was discovered that both the abberantly spliced BRAF isoforms that included a 3-nucleotide insert between exon 4 and 5 and another isoform that excluded exon 14 and 15 had increased expression in BRAF V600E melanoma and drug-resistant melanoma. This suggests that alternative splicing may be a regulatory mechanism that contributes to the oncogenic characteristics of BRAF V600E melanoma and drug-resistance. |
| Genre | Thesis |
| Topic | BRAF V600E |
| Identifier | http://hdl.handle.net/1957/55983 |
