DASAR-DASAR BIOLOGI SEL

Prof. Adi Koesoema Aman .

Divisi Hemato-onkologi Departement Patologi
Klinik FK USU /RSUP H.Adam Malik Medan .
Normal Cell Cycle & Controls

Rb
p53, p21
route to apoptosis
role of DNA repair
Rb protein: the first major checkpoint
 pRB- retinoblastoma protein
named so because in retinoblastoma cancer both alleles of
the gene are mutated so no protein is produced

pRb prevents the cell from dividing or progressing through

the cell cycle when DNA is damaged.

Control occurs at S (DNA synthesis phase) because

pRb binds and inhibits transcription factors of the E2F family

When pRb is ineffective at this role, mutated cells

can continue to divide and may become cancerous.
 pRB regulation depends on
phosphorylation
pRb can actively inhibit cell cycle progression when it is
dephosphorylated

Therefore phosphorylation inactivates its function.

At the end of mitosis (M phase) pRB depends on a

phosphatase to dephosphyorylate it , allowing it to
bind to E2F
 pRb the Master Controller : The First
Checkpoint

Robert A. Weinberg, How Cancer Arises, Scientific American 275(3):62-70,

September 1996.
 Phosphorylation of pRb
by cyclin/cyclin-kinase
complexes allows
release of pRb-bound
transcription factors
such as E2F. Now free,
the transcription factors
can alter expression of
genes necessary for cell
growth and DNA
synthesis.

Rachel A. Freiberg, Susannah L. Green, Amato J. Giaccia

Hypoxia and Cell Cycle
In: Cell Cycle Checkpoints and Cancer
Mikhail V. Blagosklonny, Ed.
ISBN: 1-58706-067-1
p53: the second major checkpoint
 p53, p21 & The Second Checkpoint

Robert A. Weinberg, How Cancer Arises, Scientific American 275(3):62-70,

September 1996.
 p53

Rb

Cell Cycle www.physiomics-

Checkpoints plc.com/cell%20cycle%20model.htm
DASAR-DASAR PATOGENESIS
TUMOR .

Prof. Adi Koesoema Aman

Departement Patologi Klinik FK USU /
RSUP .H.A.Malik , Medan
PENYEBAB KANKER .

FAKTOR LINGKUNGAN . FAKTOR GENETIK

1 . VIRUS .
2 . BAHAN KIMIA .
3 . RADIASI
4 . ULTRA VIOLET .
 ONKOGENESIS

Growth promoting Tumor suppressor

oncogenes Caretaker genes
genes
Activation/ Inactivation
amplification Mutations
Mutations

Transformation
Uncontrolled growth,
Abn biol behaviour
Maturation arrest
Abnormal diff
 HUBUNGAN ONKOGEN DENGAN
KANKER .
1. Onkogen yang sama dapat dijumpai pada banyak
jenis vertebra maupun invertebra .
2. Gen diaktivsasi pada berbagai jenis kanker manusia .
3. Akibat aktivasi onkogen pada sel dominan on –
kogen teraktivasi tersebut dapat merangsang
pertumbuhan sel walaupun dlm sel tsb ada gen yg
sama baik normal maupun inaktip .
4. Setiap onkogen akan menyandi protein yg masing2
berperan dlm transduksi signal ke inti sel utk
proses Proliferasi & Diferensiasi sel .
KARSINOGENIK

DNA SEL

KANKER
 BUKTI – BUKTI DARI KONSEP DIATAS
1. Jenis kanker tertentu inseidennya secara
langsung bergantung dengan faktor heriditer .
2. Insiden yg tinggi thd individu dgn kelainan heriditer
dalam kemampuannya memperbaiki lesi DNA .
3. Adanya kelainan kromosome pada kanker .
4. Adanya onkogen yg dpt mentransformasikan sel
normal menjadi ganas .
5. Defect Tumor Supresor Gen Transformasi Ganas
 Oncogenesis - Chemical Signaling and Cancer
Basic Concepts
Tumor
Benign (self contained)
Malignant (migratory, prone to seeding tumors at other sites)
Hypertrophy - hypertrophic cells; hyperplastic tissue
Neoplasia - new, often irregular, growth or tissue

Proto-oncogenes = Normal gene precursors of oncogenes

I
V
Mutational Agents
I
V
Oncogenes = Gene associated with abnormal cell growth

Oncogene Product = Expressed protein coded by an oncogene

Mutagens
Radiation, Chemical - tend to be small changes, insertions, deletions, or base changes

Chromosome Rearrangements (in meiosis) - can be large changes, deletions, inversions

Viral Rearrangement - viruses can become lysogenic & excise & carry genes or foreign
promoter DNA to subsequent cellular hosts where these insert into non-homologous sites
& are expressed in a non-regulated or inappropriately regulated fashion, often leading to
oncogenesis via disruption of the normal events of the cell cycle or cell cycle regulatory
points.