The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 41

are oncogenic in humans (Hepatitis B virus, Epstein-Barr virus), but most
are only tumourigenic in other species. The oncogenes of DNA viruses dif-
fer from those of retroviruses and their transforming genes have not yet
been shown to have proto-oncogenes homologous within the normal human
genome, except for a few including the presence of BLC2 sequences in the
Epstein-Barr virus (EBV) BHRF1 gene.
The Myc oncogenes are a group of well-known oncogenes. It is believed
that the majority of human cancers have a deregulated Myc ( c- Myc,
N- Myc, L- Myc ) [48,49]. Some researchers have mentioned a relationship
of 70% [50]. This oncogene encodes transcription factors that bind to DNA,
driving the expression of a vast number of target genes. The biological
outcome is enhanced proliferation (which is counteracted by apoptosis),
angiogenesis, and cancer. Myc is sufficient to drive cells into S-phase from
a quiescent state. On the other hand, it also induces cell death by apopto-
sis, which is thought to reflect a cellular defense against illegitimate cell
proliferation [51,52].
Oncogenes encode proteins called oncoproteins , which have lost impor-
tant regulatory constraints on their activity, and do not need external
activation signals [53]. Oncoproteins associated with the inner surface
of the cellular membrane are encoded members of the largest group of
oncogenes that includes the src and ras families of gene types [53]. The main
classes of oncoproteins include growth factors (HSTF1, INT2, PDGFB/SIS,
WNT1, WNT2, WNT3, etc.), tyrosine kinases (FMS, EGFR, KIT, MET,
HER2/NEU, RET, TRK, SRC), serine-threonine kinases (AKT1, AKT2),
membrane-associated guanine nucleotide binding proteins (HRAS, KRAS,
NRAS), cytoplasmic regulators (CRK), cell cycle regulators (INK4A, INK4B,
CYCLIN, D1, CDC25A, CDC25B), transcription factors (BCL3, E2F1, ERBA,
ETS, FOS, JUN, MYB, MYC, REL, TALI, SKI), intracellular membrane factor
(BCL2), RNA binding proteins (EWS), and others; and these act at different
points in signaling pathways [18]. Oncogene activation is mainly the result
of somatic events rather than hereditary causes transmitted by mutation
in the germline.
Tumour Suppressor Genes
The existence of tumour suppressor genes was first suggested in studies of
rare inherited cancer syndromes. In familial retinoblastoma, for example, a
genetic change was inherited through the germline, but mutation or ablation
of the other allele on the homologous chromosome was required for tumour
development (Knudson's two hit hypothesis) [54,55]. In sporadic cases,
independent mutational events in both homologous genes are required. As
a result, sporadic retinoblastoma is less common than the familial form [56].