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Spring, 2004 Lecture Outline

5/11 TUMORIGENESIS AND TUMOR VIRUSES


Intro: neoplasm = new tissue = tumor

organized tumor c no potential to spread = benign
disorganized tumor c potential to spread = malignancy
spread to other sites = metastasize

transformation: complex set of events- initiation, promotion, transformation- stable changes of chromosomes

viral tumor formation:

some viruses stim cell proliferation s other alterations = benign
E.g.: warts by papilloma, some tumors by poxviruses

malignant: cell proliferation + changes in cytoskeleton, membranes; chromosomal changes may occur as well

tumor types- based on tissue of origin

carcinomas = epithelial tissue
sarcomas = connective tissue
leukemias = circulating cells of lymphatic system
lymphomas = solid tumors of lymphatic system

signs of transformation in culture:

surface changes; transcription; enzyme phosphorylation

many transformed cell lines of many types of tissue

study characteristics & differences from normal cells


DNA tumor viruses: Papova; adeno; herpes; pox

general characteristics:
productive infection -> cell lysis
nonproductive infection -> transformation
inefficient ratio: 106-107 virions/transformation event

contrasts c RNA viruses:

productive infection & nonproductive -> transformation
efficient ratio: 102-104 virions/transformation event

**factors which limit DNA virus production -> incr. transformation

UV; temp change; chemicals

polyoma & friends: polyoma & SV40- non-oncogenic in normal host

culture characteristics

T-antigens: appear essential for stable transformation

fxns of small t, middle T & large T antigens

polyoma & SV40 may use different mechanisms of stimulating resting host cells into dividing & transforming

adenoviruses: different types in relation to freq. of oncogenesis

transform nonpermissive cells

only part of viral genome found retained in transformed cells

T antigens: 5 distinct proteins

herpesviruses: cause of many human & animal tumors; transformation by

defective virus, entire genome need not be present

EBV- thought to cause Burkitt's lymphoma, nasopharyngeal carcinomas

HSV-2 & cervical cancer: epidem assoc.

HHV-8 assoc. c Kaposi's sarcoma- endothelial cell lining lymph vessels

still debated- other viruses may be involved


RNA tumor viruses
: Retroviruses

RNA viruses important in discovery of proto-oncogenes

sarcoma viruses- form solid tumors
leukemia viruses- transform blood cells

integration required for transcription- true for most

lentiviruses- integration not required

avian sarcoma viruses: Rous sarcoma virus

src- sequences required for transformation
must be functional & must fxn continuously

src protein- phosphokinase: tyr instead of ser or thr

multistage transformation process

for examples of other types of oncogenes: see Wagner, Table 20.1

murine sarcoma virus- Moloney strain:

combination of viral promoter for transcription + cellular
proto-oncogene -> transformation

v-mos: protein-serine kinase

tumor growth factors(TGF): removal of TGF reverses transformation

leukemia viruses: acute vs. chronic

acute: all are recombinants of cellular genes & retrovirus cause rapid & severe leukemias

chronic: slow transformation; difficult to demonstrate means of transformation

 

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 Updated 1/25/04 by thatcher@sonoma.edu