Biokimia Kanker :

Karsinogen, Onkogen & Gen Supresif Tumor

F. Ferdinal

Dept. Biokimia dan Biologi Molekuler

Fakultas Kedokteran
Universitas Tarumanagara
 Pendahuluan
 Kanker dikenal sudah sejak lama sekali !

 Mesir (-2500 SM): osteosarkoma pada mummi.

 Hipocrates (-400 SM) : imbalans antara black humor

dan 3 body humors - natural (alamiah).

 Sir Percivall Pott (1775): kanker skrotum.

 T. Boveri (1914): lesi pada DNA akibat mutasi somatik.

 Broca (1866): kanker payudara dan kanker hati akibat
kelainan yang sifatnya herediter.
 Peyton Rous (1910): RSV menyebabkan kanker – v-src.
 Bishop & Varmus (1976): v-src punya pasangan homolog
di dalam sel normal – c-src.
 Henry Harris (1969): Gen supresor tumor, berperan dalam
mengendalikan pertumbuhan sel.
 Kanker : adalah penyakit genetik (transformasi ganas)

Cancer is a genetic disease at celular level

Perubahan pada transformasi ganas
 Perubahan biokimia
 Perubahan bentuk sel
 Hilangnya inhibisi kontak pertumbuhan
 Hilangnya inhibisi kontak pergerakan
 Hilangnya ketergantungan pada penjangkaran
 Perubahan struktur sitoskeleton
 Berkurangnya kebutuhan faktor pertumbuhan
Molecular Basis of Cancer Phenotypes:

1 Immortality ( Telomereae & GST)

2 Decreased Dependence on Growth Factors to
Support Proliferation,
3. Loss of Anchorage-Dependent Growth and
Altered Cell Adhesion,
4 Cell Cycle and Loss of Cell Cycle Control,
5 Apoptosis and Reduced Sensitivity to Apoptosis
6 Increased Genetic Instability
7 Angiogenesis
Six major features of cancer cells
Some biochemical and genetic changes occurring in human cancer cells
The cell cycle showing checkpoints at which DNA is monitored
before the next stage of the cycle is entered
The Ames Test to screen for mutagens
Some ways in which proteins encoded by oncogenes work. The Figure shows examples of various
proteins encoded by oncogenes. The proteins are listed below with the corresponding oncogene
given in parentheses along with its OMIM number. A growth factor, FGF 3 (INT2,164950); a growth
factor receptor, [EGFR] (HER1, 131550); a G protein (H-RAS-1, 190020); a signal transducer (BRAF,
164757); a transcription factor (MYC,190080); a tyrosine kinase and involved in cell-cell adhesion
(SRC, 190090); a cell cycle regulator (PRAD, 168461); a regulator of apoptosis (BCL2, 151430).
Burkitt’s Lymphoma
CML
Point Mutation
3. Genes involved in DNA repair
• Peroderma pigmentosum,
• Ataxia telangiectasia,
• Fanconi’s anemia and
• Bloom’s syndrome

4. Epigenetic
•Metilasi DNA
•Genomic Imprinting
 The overall progression to malignancy is
therefore a complex event.
Some Genes Associated with Colorectal Carcinogenesis