Origin of viral Oncogenes

Regardless of how oncogenes induce cancers, it how seems

clear that retroviral oncogenes have evolved from normal cellular
protooncogenes. originally, it was thought that the cellular homologs of
viral oncogenes might be relics of integrated retroviral proviruses.
However, this is clearly not the case. Comparisons of the nucleotide
sequences of viral oncogenes and the homologous cellular
protooncogenes have shown that these genes share major regions of
the sequence identity. The key difference is that the cellukar
protooncogenes contain intron, whereas viral oncogenes are single
exons. This is not consistent with the idea that cellular protooncogenes
have evolved from v-oncogenes on integrated proviruses. Instead, it
strongly suggest that v-oncogenes are derived from ancestral cellular
protooncogenes. This difference is to be expected if the v-oncogenes
evolved from cellular protooncogenes the retroviral genomes are RNA
and the intron sequences of RNA transcripts of protooncogenes should
be splice out during RNA processing. All the needs to occur is for an
mRNA copy of a protooncogene to be ligated into the RNA genome of a
retrovirus by a recombination mechanism that preserves the LTR
regions of the viral genome. The viral reverse transcriptase will then
convert the mRNA-viral RNA hybrid into homologous DNA for
intregation into the host genome.
In some case, different retroviruses that infect distantly related
species have acquired copies of the same cellular protooncogene. In
other case, closely related viruses contain oncogenes derived from
completely unrelated cellular protooncogenes.
By comparing the nucleotide sequences of the v-oncogenes and
the homologous c-protooncogenes, the sites of the of breakage and
joining in the recombination events that gave rise to the v-oncogenes
can sometimes be identified. In other cases, extensive rearrangements
have occurred, making it impossible to identify the sites or
recombination involved in the acquisition of the oncogenes by the
retrovirus. In several cases, the viral oncogenes encode fusion proteins
containing part of the gag protein and the oncogenes product. In most
cases, the retroviral acquisition of an oncogene has been accompanied
by the loss of viral genetic material required for replication. Such
defective viruses can integrate normally as proviruses, but can only
produce progeny viruses in the presence of a helper virus that
provides the missing function .

CANCER AS THE END PRODUCT OF A MULTISTEP PROCESS

Finally, we should emphasize that a large amount of data

indicates that the cancerous state is the end product of a multistep
process. The cell lines used in transfection experiment are probably
already at some intermediate stage in the pathway, possibly simply
due to the selection for the ability to grow under cell calture conditions.
The oncogenes-induced transformation observed in cell cultures is
undoubtedly only one part of a more complex pathway.
In fact, there is considerable evidence indicating that certain
oncogenes may have cooperative effect in promoting neoplastic
transformation. Moreover, different oncogenes seem to play different
roles in oncogenic pathways in different cell types. Finally, seems likely
that different molecular events are involved in the acquisition of the
enhanced proliferative capacity of cells, in the ability of tumors to
invade adjacent tissues, and in the capacity for metastasis. To what
extent and in what roles protooncogenes and oncogenes are involve in
these processes in human cancers remain to be determined.
Regardless of the extent of their involvement in the formation of
malignant tumors, the ongoing and future investigation of
protooncogenes and oncogenes promise to yield important information
about the molecular circuitry that controls cell proliferation in higher
eucaryotes such as humans.