DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA

Stéhelin, D; Varmus, Harold; Bishop, J. Michael; Vogt, Peter K.

doi:10.1038/260170a0

Cited by 1,190 publications

(536 citation statements)

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“…After the discovery of the 'cancercausing' sarcoma virus by Rous in 1909 3,4 research into genetics continued and the hypothetical gene thought to be responsible for a cell becoming cancerous was named an oncogene 5 . In the 1960s the src (sarcoma) oncogene was discovered in Rous's sarcoma virus (RSV) 6 and in 1975 this oncogene was found in not only cancerous cells 7 , but also in normal healthy cells 8 . This led researchers to hypothesize that the src oncogene was triggered to become cancerous by the introduction of the virus into the cells.…”

Section: Cancermentioning

confidence: 99%

Role of the pro-survival molecule Bfl-1 in melanoma

Hind

Carter

Harris

et al. 2015

The International Journal of Biochemistry & Cell Biology

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Melanoma, the cancer derived from the melanocytes of the skin, is becoming an ever more common cancer in the ageing population of the developed world and displays an intrinsic resistance to current therapies. This chemo resistance makes metastatic melanoma an extremely difficult cancer to treat leading to a 5 year survival rate of just 20%. As such, it is important to unearth new potential drug targets to increase the prospects for melanoma patients.Bfl-1 is a pro-survival protein of the Bcl-2 family of apoptosis regulating proteins. It has been found to be over-expressed in a small subset of chemo resistant tumours, including melanoma. Accordingly, I characterised the molecule in melanoma cells and determined its role in protecting these cells from chemotherapy-induced apoptosis. I elucidated the expression profile and half-lives of the protein and mRNA across a panel of melanoma cell-lines and healthy melanocytes. I also confirmed, using pathway specific inhibitors, that Bfl-1 was transcriptionally regulated by the NFB pathway and concluded through pulsechase experiments that Bfl-1 protein was degraded, at least in part, by the proteasome. Subcellular fractionation and indirect immunofluorescence techniques elucidated that Bfl-1 was located mostly at the mitochondria in both resting and apoptotic cells, with a diffuse level present throughout the cytoplasm. As well as characterising the protein in both melanoma cells and healthy primary melanocytes, I determined its role in the resistance of these cells to apoptosis. Over-expressed Bfl-1 was found to protect melanoma cells from apoptosis caused by a range of chemotherapeutic agents in A375 melanoma cells, which naturally expressed very low levels of Bfl-1. Further, knock down of Bfl-1 using siRNA technology in melanoma cells revealed the dependence of these cells on Bfl-1 for their resistance to certain chemotherapeutic agents currently used in melanoma treatment, including the MEK inhibitor PD901. All together, this research contributes to our understanding of Bfl-1 and highlights it as a potentially important therapeutic target in metastatic melanoma.

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Section: Cancermentioning

confidence: 99%

Role of the pro-survival molecule Bfl-1 in melanoma

Hind

Carter

Harris

et al. 2015

The International Journal of Biochemistry & Cell Biology

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“…c-src was ®rst isolated as the normal cellular homologue of v-src, the transforming gene of Rous Sarcoma virus (Stehelin et al, 1976). As the ®rst proto-oncogene described and one of the ®rst molecules demonstrated to have tyrosine kinase activity, Src has provided a prototype for understanding signal transduction involving tyrosine phosphorylation.…”

mentioning

confidence: 99%

The many faces of Src: multiple functions of a prototypical tyrosine kinase

1998

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“…The first oncogenes were characterized in animal retroviruses and are believed to have derived from normal cellular genes which have become integrated into viral genomes (Duesberg, 1983;Stehelin et al, 1976;Spector et al, 1978;Bishop, 1981;Scolnick et al, 1973;Scolnick & Parks, 1974). The ability of the viral oncogenes to transform may result from inappropriate expression of a normal gene product (Huebner & Todaro, 1969;Vande Woude et al, 1980), or from subtle differences between the viral oncogenes and their cellular counterparts (Schwartz et al, 1983;Takeya & Hanafusa, 1983;Ellis et al, 1982;Dhar et al, 1982;Capon et al, 1983).…”

Section: Vol 226mentioning

confidence: 99%