Rous sarcoma

The Rous sarcoma is a form of cancer produced by RSV (Rous sarcoma virus) which
usually infects chickens. RSV was first discovered in 1911 by Peyton Rous (5 Oct. 1879
16 Feb 1970), who was an American researcher at Rockefeller University in New York.
Fifty-five years later he was awarded a Nobel Prize in Physiology or Medicine for his
discovery.

About RSV

RSV is a retrovirus=virus with RNA form the Retroviridae family which utilises an
enzyme, called reverse transcriptase to copy RNA into DNA (Neago, Creu and Mierl,
2014).

RSV is an oncovirus because it

causes sarcoma(fig1.0) =a tumour,
often highly malignant, composed
of cells derived from connective
tissue such as bone, cartilage, muscle,
blood vessel, or lymphoid tissue.
(TheFreeDictionary.com, 2016) Fig 1.0 Sarcoma cells under a microscope
(Treatcancer.com, 2016)

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The Rous sarcoma virus(fig.1.1) contains RNA, 10

molecular weight units or about 1 per cent by weight, but

no DNA (Crawford and Crawford, 1961) (Dobson,
Richard L. Montagna, William, 2013).

Fig 1.1 RSV (Flax.nzdl.org, 2016)

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 RSV has only 3 genes (gag, env and pol), but a gene it takes from the hosts genome
makes it an oncogenic virus: src (fig2.0).

Fig 2.0

Each of the three genes has a different role: while gag and env encode proteins for the
capsid and the envelope, pol synthesizes the reverse transcriptase enzyme. The src gene
encodes a tyrosine kinase, an enzyme that attaches phosphate groups to Tyr residues on a
variety of host cell proteins. (Biology-pages.info, 2016) The gag gene is terminated by an
amber stop codon and is contained within a different reading frame than is the pol gene.
The pol and env genes overlap. (Ncbi.nlm.nih.gov, 2016)

The cellular gene (c-src) differs in two ways from the viral gene (v-src):

c-src is a split gene, containing multiple exons separated by introns; v-src is not
split.
v-src genes always contain mutations that distinguish them from the c-src of the
chicken. (Biology-pages.info, 2016)

The Schmidt-Ruppin or the B77 strain of Rous sarcoma virus (RSV) was inoculated into
limb buds of 4.5-days-old avian embryos. No sarcoma but blister formation was observed
in those RSV-inoculated embryos. Protein kinase activity of pp60 v-src in RSV-inoculated
embryos, even in the site of virus inoculation, was the same as that in mock-infected
embryos. This indicated that the expression of the v-src gene did not attain superiority over
that of the c-src gene in RSV-inoculated embryos. The v-src gene was detected in every

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DNA from tissues of RSV-inoculated embryos but not in DNAs from tissues of RSV-
inoculated chicken except for the DNA from Rous sarcoma. Those results confirmed that
the lack of sarcoma induction in early avian embryos by RSV was due to the lack of the
expression of the v-src gene which was present in the target cells. (Ncbi.nlm.nih.gov, 2016)

The src gene is not necessary for the RSVs survival: Whenever the DNA of RSV
happens to insert itself near the c-src gene of its host, RNA polymerase II might
occasionally read past the end of the env gene and transcribe the c-src gene as well. The c-
src introns would be removed by normal RNA processing, producing a mRNA encoding
the four genes. Before RSV becomes oncogenic it needs certain mutations. (Biology-
pages.info, 2016)

About the tumour

Morphologically the tumors produced by RSV in all susceptible species have been
classified as undifferentiated sarcomas or myxosarcomas. In the native host, the chicken,
the tumor is usually progressive, metastasizing and lethal, though sometimes after a period
of growth the tumor regresses and disappears, particularly in older birds (Rous, 1911)
(Dobson, Richard L. Montagna, William, 2013).

According to the original description (Rous, 1910a) the sarcoma consists of loose
bundles of spindle-shaped cells (fig. 3.0) running in every direction and separated from the
lesser blood vessels only by endothelium.
Where such a bundle is cut transversely, the
appearance is that of a group of round cells of
varying sizes. Intercellular fibrils are
demonstrable, though rare in the more cellular
portions of the growth. The spindle cells,
although in general large, vary much in size and
shape, some are short and plump, some
continued into long slender processes. The
nucleus is, as a rule, large and vesicular with a loose network and several coarse masses of

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chromatin. Mitosis is fairly frequent and cells with two to five or six nuclei occur.
(Auchter, E. C. Avery, Georges S. Beadle, G. W.)
Reflecting on his career in his Nobel Prize lecture, Rous credited Linnaeus with opening a
wide door for him into natural history, which eventually led him to his study of cancer.
Rous, in turn, opened a wide door for countless others into the field of tumor biology. (Van
Epps, 2016)

References

Neago, D., Creu, R. and Mierl, D. Fig 3.0 Invasion of muscle by the Rous sarcoma.
The spindle-shaped cells surround the muscle
(2014). retrovirus. In: Genetics Dictionary, fibers which appear round in cross section.
(Courtesy of the Journal of Experimental
p.146. Medicine) (Auchter, E. C. Avery, George S.
Beadle, G. W.)
-ALL

TheFreeDictionary.com. (2016). sarcoma. [online] Available at: http://medical-

dictionary.thefreedictionary.com/sarcoma

Treatcancer.com. (2016). [online] Available at: http://www.treatcancer.com/wp-

content/uploads/2015/12/Kaposi_sarcoma_high_mag-1030x687.jpg

Dobson, Richard L., Montagna, William. (2013) Carcinogenesis. Chapter VIII: Tumor
Viruses, II Rous sarcoma virus, ProQuest EBook Central. Web. p. 135-136

-Elsevier Science

Ncbi.nlm.nih.gov. (2016). Nucleotide sequence of Rous sarcoma virus. - PubMed -

NCBI. [online] Available at: https://www.ncbi.nlm.nih.gov/pubmed/6299578

Biology-pages.info. (2016). The Rous Sarcoma Virus (RSV). [online] Available at:
http://www.biology-pages.info/R/RSV.html

Ncbi.nlm.nih.gov. (2016). Rous sarcoma virus does not induce sarcoma in early chick
embryos by lack of the v-src gene expression. - PubMed - NCBI. [online] Available at:
https://www.ncbi.nlm.nih.gov/pubmed/1336425

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 Flax.nzdl.org. (2016). Virology v1. [online] Available at:
http://flax.nzdl.org/greenstone3/flax;jsessionid=EF4DF1B36066AB8BBB8AAB35CC250
D1A?
a=d&c=virology1&d=HASH017b6fd1485c699564d72d81&dt=simple&p.a=b&p.s=Classif
ierBrowse

Auchter, E. C. Avery, George S. Beadle, G. W. (2013) Survey of Biological Progress.

Chapter VI: Virus Tumors, V Rous sarcoma number 1. ProQuest EBook Central. Web. p
180-181

-Elsevier Science

Van Epps, H. (2016). Peyton Rous. [online] Available at:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213042/