Mn hc: Sinh hc phn t trong lnh vc sc khePROTO - ONCOGENEGV hng dn: TS. NGUYN HONG CHNGHc vin: Phan Th Kim AnhNguyn Minh Ti LcL Trng NghaNguyn L Phng QuynLp: Cao hc Di truyn K24

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Khi nim v proto oncogeneC ch kch hot proto oncogene thnh oncogeneGene RasGene EGFR Gene C MYCGene C SIS

NI DUNG

1. Khi nim v proto oncogeneLch s pht hin oncogene

Nm 1911: Peyton Rous pht hin ra virus c kh nng gy ung th gia cm (RSV)

Sau , nhiu nh khoa hc cng chng minh c ha cht v tia x gy ung th.

1972: Graham v van der Eb dng dng t bo NIH 3T3 pht hin ra t bin trn gen

1. Khi nim v proto oncogeneProto oncogene: l cc gen bnh thng trong c th m ha cho cc protein iu ha s pht trin ca t bo, s tng sinh v bit ha ca t boProto oncogene c th tr thnh oncogene do t bin hay l do s biu hin vt mc

Phn loi proto oncogene1. Khi nim v proto oncogene

1. Khi nim v proto oncogene

t bin gen: gene mt chc nng hay biu hin qu mc

Khuch i ca gene: theo nhiu c ch lm gia tng hot ng gene

Chuyn v gene (ti sp xp NST): Gene b gn vo promoter hot ng mnh Promoter hot ng mnh chuyn vo nh hng ti hot ng miRNA

Ngoi ra, c nhiu bo co chng minh epigenetic l mt yu t tc ng trong qu trnh hot ha cc proto oncogene thnh cc oncogene.

2. C ch kch hot proto oncogene thnh oncogene

2. C ch kch hot proto oncogene thnh oncogene

2. C ch kch hot proto oncogene thnh oncogene

2. C ch kch hot proto oncogene thnh oncogene

3. Gen EGFREGFR l t ting anh vit tt Epidermal growth factor receptor Th th yu t tng trng biu b (EGFR), cn c gi l ErbB1/HER1. EGFR l mt th th tyrosine kinase (RTK) thuc h ErbB / HER.

Cu trc: 3. Gen EGFR

Mt s loi liganEGF,TGF-, Betacellulin (BTC),Epiregulin (EPR), Heparin gn EGF nh tng trng yu t (HB-EGF) Amphiregulin

3. Gen EGFR

C ch hot ngBa con ng truyn tn hiu ch yu:RAS-RAF-MEK-ERKPI3K_AKT PLC-PKC.

3. Gen EGFREGFR_Cancer

Tng biu hin qu mc EGFR, Tng tit (t tit/cn tit) ligand.Bt cp cho cc receptor khc loi.Gim biu hin EGFR.EGFR t bin.

3. Gen EGFRTng biu hin qu mc EGFRHot ng ri lon EGFR lin quan ti biu hin qu mc EGFR.Khuych i gen EGFR: tng cng hot ng cc promoter EGFR hoc kh yu t iu ho phin m v sau phin m.

3. Gen EGFRTng tit (t tit/cn tit) ligand

TGF- v EGF thng xuyn ng biu hin cng vi EGFR trong cc loi ung th khc nhau.

T BIN EGFR3. Gen EGFR

t bin EGFR chia thnh 3 nhm t bin chnhVng ngoi t bo chtTrong tyrosine kinaseVng trong t bo cht

T BIN EGFR3. Gen EGFRVng ngoi t bo chtReceptor t binTn sutLoi ung thEGFRvIMt u_N Him U noEGFRvIIMt exon 14-15HimU noEGFRvIIIMt exon 2-7ThngU no, UT tuyn tuyn lit, UT v, UT phi khng t bo nh (NSCLC), UT c hng,

Vng trong t bo chtT BIN EGFR

Receptor t binTn sutLoi ung thEGFRvIII/12-13Mt exon 2-7 v 12-13Him U noEGFRvII.TDM/2-7t bin lp oan exon 2-7HimEGFRvIVMt exon 25-27HimEGFRvVMt exon 25-28HimEGFR.TDM/18-25/26t bin lp on 18-25/26Him

3. Gen EGFR

3. Gen EGFRTrong tyrosine kinaseReceptor t binTn sutLoi ung thG179A/Ct bin imHim UT phi khng t bo nh746-753-DELMt bin th nhThng gp766-768-INSMt bin th nhHimL858Rt bin imThng gpL861Qt bin imHim

T BIN EGFR

Gim iu ho receptor li3. Gen EGFRTn hiu EGFR khc thng do gim iu ho receptor li dn n t bo bin i thnh khi u

3. Gen EGFR

Gim iu ho receptor li

3. Gen EGFREGFR bt cp cho

Chc nng ca EGFR trong t bo ung th khng ch b hp l mt th th trn b mt t bo. S tng tc cho c m t gia EGFR v mt thnh vin khc ca h ErbB, nh l TKR, cc phn t bm dnh t bo, cytokine recepter, knh ion, G protein couple recepter (GPCR).

Gene Ras l h u tin c pht hin ca G protein, c 3 h gene Ras ph bin ngi l H, K, N Ras.Protein Ras l mt GTPase tham gia vo qu trnh truyn tn hiu t bo4. Gene Ras

4. Gene RasCu trc protein Ras

4. Gene Ras

Vai tr ca protein Ras trong qu trnh truyn tn hiu

4. Gene RasVai tr ca protein Ras trong qu trnh truyn tn hiu

Hu ht cc t bin l cc t bin im4. Gene Ras

t bin gene Ras

4. Gene Ras

t bin gene Ras ti v tr codon 12

5. Gen MycH gen MYC oncogene c vai tr quan trng trong nhiu bnh ung th ngi ngi, Myc nm trn NST 8 v iu ha biu hin khong 15% tng s cc gen thng qua vic gn vo trnh t E-Box t iu ha s phin mCc proto-oncogene, MYC, l trung tm ca nhiu con ng truyn tn hiu v l mt gen p ng u ca phc hp receptor ligand-mng S biu hin ca MYC c iu ha mt cch cht ch nh vic kim sot s lng cc c ch lin quan n iu ha phin m trong khu vc gn promoter ca n

5. Gen Myc- nhn t iu ha phin m

5. Gen Myc

Vai tr ca Myc trong con ng apoptosis

5. Gen Myc

H gene SIS oncogene c vai tr trong nhiu bnh v ung th ngi, thng c nhc n qua cc gene nh: c-sis hay v-sis. ngi Sis nm trn NST 22 v iu ha vic biu hin gene thng qua cu trc Triplex forming oligonucleotides (TFOs) nhn bin v gn vo trnh t trn duplex DNA v kt hp vi receptor kch thch s phin m.Cc proto-oncogen, SIS, l cht p ng ca con ng truyn tn hiu qua PDGFR- cellular membrane. S biu hin ca SIS lun i cng vi con ng truyn tnh hiu ca PDGFR-.6. Gene Sis

Triplex forming oligonucleotides (TFOs)

6. Gene Sis Platelet-derived growth factor

c-sis proto-oncogene m ha cho protein c-Sis c cu to t 2 chui B hoc t mt A chain v mt B chain nn c kh nng lin kt vi PDGFR ( receptor)

PDGF l mt nhm thuc nhn t kch thch s pht trin ca t bo. PDGF receptor (PDGFR) c cu to t chui v chui , n c 3 dng PDGFR nh hnh bn

Theo nh l thuyt th PDGF c th tng tc vi PDGFR nh hnh u tin, tuy nhin trong thc t, cu trc PDGF c chng minh c th tng tc vi PDGFR th rt t: PDGF-AA v PDGF-CC tng tc vi PDGFR-; PDGF-BB tng tc vi PDGFR-

6. Gene Sis Platelet-derived growth factor

Con ng c ch apoptosis6. Gene Sis

Nh vy, proto oncogene tht ra l cc gene bnh trng trong c th, sau khi t bin hay do biu hin qu mc chuyn chng thnh oncogene

Cc c ch c bn lin quan ti vic chuyn proto oncogene thnh oncogene bao gm t bin gene, s khuch i ca gene v s chuyn v gene. Ngoi ra, c th do hin tng epigentic

Tuy nhin, ngoi oncogene th cn c mt nhm gene quan trng khc l tumor suppressor gene v ung th l do s tch ly ca nhiu loi t bin khc nhau.KT LUN