Biokimia Kanker :

Karsinogen, Onkogen & Gen Supresif Tumor

F. Ferdinal

Dept. Biokimia dan Biologi Molekuler

Fakultas Kedokteran
Universitas Tarumanagara
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 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.

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 P. 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

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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

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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

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Six major features of cancer cells
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Some biochemical and genetic changes occurring in human cancer cells
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The cell cycle showing checkpoints at which DNA is monitored before
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The Ames Test to screen for mutagensJump to first page
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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).
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Burkitt’s Lymphoma Jump to first page
CML
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Point Mutation
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Guardian of the Genome

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3. Genes involved in DNA repair
• Xeroderma 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.
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Some Genes Associated with Colorectal Carcinogenesis
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Figure 3 Overview of APJ signalling pathways. Schematic diagram of APJ
signalling pathways. Coupling to Gq/11 stimulates PLC-β signalling,
including the hydrolysis of phosphatidylinositol 4,5-biphosphate (PIP2) to
IP3 and diacyl glycerol (DAG). DAG subsequently activates PKC, which is
an activator of the small G-protein, Ras. Ras then either activates a
cascade leading to the activation of JNK, and the transcription factors SP1
and c-Jun or the MAPK cascade of Raf-1, MAPK-/ERK kinase (MEK1/2) and
ERK1/2. ERK1/2 have a variety of substrates including numerous
transcription factors (e.g. c-Jun and c-fos) and other kinases (e.g. p70S6K).
Gq/11 also signals independently of PKC, but still via Ras and the MAPK
cascade. Gi/o stimulates the MAPK cascade via PKC, and it can also
activate phosphoinositide 3-kinase (PI3K) with the subsequent activation
of Akt and mammalian target of rapamycin (mTOR), leading to the
activation of both p70S6K and endothelial nitric oxide synthase (eNOS).
Furthermore, Gi/o signalling inhibits adenylate cyclase (AC) activity. In
contrast, Gs activates AC, increasing cAMP synthesis from ATP, leading to
the activation of protein kinase A (PKA). Thin black arrows indicate
activation pathways and the red blunted arrow indicates inhibition.
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