TRANSFORMASI

SEL
&
KARSINOGENESIS

Dwi Yanti

PENGERTIAN
Transformasi Sel
Peralihan suatu sel-sel normal menjadi
sel-sel tumor
Sel normal >> berdiferensiasi >> dihambat
pembelahannya >> banyak di fase G 0
Sel tumor >> tidak berdiferensiasi >>
membelah tanpa hambatan
Karsinogenesis
Proses terbentuknya kanker dari awal
terpapar sampai terbentuknya sel kanker.
Memiliki beberapa tahapan dan terjadi
dalam kurun waktu yang lama ( 15-25
tahun)

SEL NORMAL

growth factor
growth factor receptor

sitoplasma
transduksi sinyal

nukleus

aktivasi
transkripsi

DNA
RNA

SEL MALIGNA

Increase
in growth
factors

Increase
in growth
factor
receptors

Increase in
signal
transductio
n

Increase in
activation
of
transcripti
on

- Disturbed processes of mitosis and protein synthesis

KARAKTERISTIK
SEL
KANKER

09/28/09

MULTISTEP KARSINOGENESIS

MULTISTEP KARSINOGENESIS
Inisiasi: Mutasi pada gen yang
mengendalikan pengaturan siklus sel
(irreversible) defek protoonkogen, namun
kehilangan fungsi gen supresor tumor juga
dapat membantu terjadinya inisiasi.
Promosi: Perbanyakan sel-sel yang
terganggu karena inisiasi tumor. Proses ini
dapat berlangsung sangat lambat, hingga
bertahun-tahun.
Progresi: Proses yang menyebabkan suatu
tumor menjadi ganas melalui perbanyakan,

Multistep Carcinogenesis

REGULATORY GENE
Proto-oncogenes (activated oncogenes) code
for:
growth factors
receptors
signal-relay or transduction factors
EX: ras - colon cancer
myc - lymphoma
bcr-abl - chronic myelogenous leukemia
(Philladelphia chromosome)
Tumor suppressor genes - code for factors that
down regulate the cell cycle, promote
differentiation and supress oncogenes from causing
cancer
Rb-1 retinoblastoma gene
p53

09/28/09

Rb
Aktif:
hipofosforilasi
Inaktif:
hiperfosfolirasi
Transisi G1/S

09/28/09

Networks p53

Ling
2006.Bai and Wei Ghuo Zhu, Journal of Cancer Molecules 2(4): 141-153,

NEOPLASIA proto-oncogene is activated or

tumor suppressor gene is inactivated

normal growth oncogenesis

Activation of proto-oncogene:

point mutation
translocation
gene amplification

Also - Failure of Immune Surveillance theory :

immune system responds to neoantigens as to

foreign antigens, but neoplastic cells escape
recognition and destruction --> become clinical
cancers

PENYEBARAN TUMOR GANAS

1. Invasi
penyebaran lokal
- fase in situ
- fase invasi
Terdapat kepekaan jaringan tubuh terhadap invasi
2. Metastasis
penyebaran jauh
perjalanan : - invasi matriks ekstrasekuler
- Penyebaran vaskuler
- pertumbuhan sel tumor di tempat
baru

Invasi
1. Cellular Multiplication
2. Mechanical Pressure
3. Release of Lytic Enzym ( Protease)

Serine (Urokinase-type-plasminogen activator (uPA))

Cysteine (cathepsin B, D)

Matrix Metaloproteinase (MMP)

4. Penurunan Adesi Sel

Integrin: cell-matrix adhesion

E-cadherin/catenin adhesion complex: cell-cell adhesion

5. Cell motility/migration

Small Rho GTPase family

Motility promoting factors

Steps of
Invasion

steps
i
n
metas
1. Invasion and
ta s i s
infiltration of
destruct near
tissue

2.

3.
4.
5.

destruct far
tissue

surrounding normal
host tissue with
penetration of small
lymphatic or
vascular channels;
Release of
neoplastic cells,
either or single cells
or small clumps,
into the circulation;
Survival in the
circulation;
Arrest in the
capillary beds of
distant organs;
Penetration of the
lymphatic or blood
vessel walls
followed by growth
of the disseminated
tumor cells

Preferential metastatic
sites
Primary tumour
Common distant site (s)
Breast adenocarcinoma

Bone, brain, adrenal

Prostate adenocarcinoma

Bone

Lung small cell carcinoma

Bone, brain, liver

Skin cutaneous melanoma

Brain, liver, Bowel

Thyroid adenocarcinoma

Bone

Kidney clear cell carcinoma

Bone, liver, thyroid

Testis carcinoma

Liver

Bladder carcinoma

Brain

Neuroblastoma

Liver, adrenal

Reason for organ

selectivity
Mechanistic theory: determined by
the pattern of blood flow.
Seed and soil theory: the provision
of a fertile environment in which
compatible tumor cells could
grow

TERIMA KASIH
&
SEMOGA
BERMANFAAT