I-oncogene yisakhi sofuzo samaselula okusho ukuthi kungenzeka kukhuthaze ukukhula komdlavuza. Yiziphi izinhlobo ezahlukahlukene zama-oncogene? Yiziphi izindlela ezenziwa zisebenze? Izincazelo.

I-oncogene (evela kuma-Greek onkos, isimila nohlobo lofuzo, ukuzalwa) okubizwa nangokuthi i-proto-oncogene (c-onc) yisakhi sofuzo esikwazi ukusho ukuthi sinikeza i-phenotype yomdlavuza esitokisini esivamile se-eukaryotic. Ngempela, i-oncogenes ilawula ukuhlanganiswa kwamaprotheni ashukumisa ukuhlukaniswa kwamaseli (abizwa ngama-oncoprotein) noma avimbele ukufa kweseli okuhleliwe (noma i-apoptosis). I-Oncogenes ibhekele ukwanda kwamaseli okungalawulwa okubeka phambili ekuthuthukiseni amaseli omdlavuza.

I-Oncogenes ihlukaniswe ngezigaba ezi-6 ezihambelana ngokulandelana nama-oncoprotein abawabeka:

• izici zokukhula. Isibonelo: ama-proto-oncogene afaka amaprotheni omndeni wakwa-FGF (i-Fibroblast Growth Factor);
• transmembrane ukukhula factor receptors. Isibonelo: i-proto-oncogene erb B ekhomba i-EGF (Epidermal Growth Factor) receptor;
• Ama-G-protein noma amaprotheni we-membrane abopha i-GTP. Isibonelo: ama-proto-oncogenes omndeni wama-ras;
• ulwelwesi tyrosine protein kinases;
• ulwelwesi amaprotheni kinases;
• amaprotheni anomsebenzi wenuzi.Isibonelo: proto-oncogenes isiza A, phos, June et c-myc.

Ukuvuselelwa kwamaseli kuqinisekiswa yi umjikelezo weseli. Lesi sakamuva sichazwa ngeqoqo lezehlakalo ezikhiqiza amangqamuzana amabili endodakazi avela kuseli lomama. Sikhuluma ngakho ukuhlukaniswa kwamaseli noma "mitosis".

Umjikelezo weseli kufanele ulawulwe. Ngempela, uma ukuhlukaniswa kwamaseli kunganele, umzimba awusebenzi kahle; Ngakolunye uhlangothi, uma ukuhlukaniswa kwamaseli kugcwele, amaseli akhula ngokungalawuleki, okukhuthaza ukuvela kwamangqamuzana omdlavuza.

Ukulawulwa komjikelezo weseli kuqinisekiswa yizakhi zofuzo ezihlukaniswe ngezigaba ezimbili:

• anti-oncogenes evimbela ukwanda kwamaseli ngokunciphisa umjikelezo weseli;
• i-proto-oncogenes (c-onc) noma i-oncogenes ekhuthaza ukwanda kwamaseli ngokwenza kusebenze umjikelezo weseli.

Uma siqhathanisa umjikelezo weseli nemoto, ama-anti-oncogenes angaba ngamabhuleki kuthi ama-proto-oncogenes abe ama-accelerator akamuva.

Ukubukeka kwesimila kungavela ekuguqulweni kokusebenza kwama-anti-oncogene noma okuphambene noguquko olusebenzayo lwe-proto-oncogenes (noma i-oncogenes).

Ukwehluleka kokusebenza kwama-anti-oncogenes kubavimbela ekwenzeni umsebenzi wabo wokuvimbela ukwanda kweseli. Ukuvinjelwa kwama-anti-oncogene umnyango ovulekele ukuhlukaniswa kwamaseli okungalawulwa okungaholela ekubonakaleni kwamaseli amabi.

Kodwa-ke, ama-anti-oncogene yizakhi zofuzo zeselula, okungukuthi, akhona ngokufana kuma-chromosomes amabili awathwala ku-nucleus yeseli. Ngakho-ke, lapho ikhophi eyodwa ye-anti-oncogene ingasebenzi, enye yenza kube lula ukusebenza njenge-brake ukuze isihloko sivikeleke ekwandeni kwamaseli nasengozini yamathumba. Lokhu kunjalo, ngokwesibonelo, zofuzo lwe-BRCA1, ukuguqulwa kokuvimbela okuveza umdlavuza webele. Kepha uma ikhophi lesibili lalesi sakhi sisebenza, isiguli sihlala sivikelekile yize sithonywe ngenxa yekhophi lokuqala elingalungile. Njengengxenye yokuthambekela okunjalo, kwesinye isikhathi kubhekwa ukuvimbela i-mastectomy ephindwe kabili.

Ngakolunye uhlangothi, ukuguqulwa okusebenzayo okuthinta ama-proto-oncogenes kugcizelela umphumela wazo ovuselelayo ekwandeni kweseli. Lokhu kwanda kwamaseli anarchic kubeka phambili ekukhuleni komdlavuza.

Njengama-anti-oncogenes, ama-pro-oncogenes ayizakhi zofuzo zeselula, akhona ngokufana kuma-chromosomes amabili awaphethe. Kodwa-ke, ngokungafani nama-anti-oncongens, ukutholakala kwe-pro-oncogene eyodwa eshintshiwe kwanele ukukhiqiza imiphumela esabekayo (kulokhu, ukwanda kweseli). Isiguli esiphethe lokhu kuguquka sisengozini yomdlavuza.

Izinguquko ku-oncogenes zingazenzakalela, zizale njengefa noma zibangelwe ngama-mutagens (amakhemikhali, imisebe ye-UV, njll.).

Izindlela eziningi zisuselwa ekusebenzeni kokuguqulwa kwama-oncogenes noma ama-pro-oncogenes (c-onc):

• ukuhlanganiswa kwegciwane: ukufakwa kwegciwane le-DNA ezingeni lohlobo lokulawula. Lokhu ngokwesibonelo icala le-human papillomavirus (HPV), elidluliselwa ngocansi;
• ukuguqulwa kwamaphoyinti ngokulandelana kofuzo olufaka iprotheni;
• ukususwa: ukulahleka kocezu olukhulu noma oluncane lwe-DNA, okuyimbangela yokuguquka kwezakhi zofuzo;
• ukuhlela kabusha kwesakhiwo: ukuguqulwa kwe-chromosomal (translocation, inversion) okuholela ekwakhiweni kofuzo lwe-hybridi olufaka iprotheni engasebenzi;
• ukukhulisa: ukuphindaphindwa okungajwayelekile kwenani lamakhophi wesakhi esisele. Lokhu kukhuliswa ngokuvamile kuholela ekwandeni kwezinga lokuvezwa kofuzo;
• ukwehliswa kwesimo se-RNA: izakhi zofuzo zinqanyuliwe endaweni yazo ejwayelekile yamangqamuzana futhi zibekwe ngaphansi kokulawulwa okungafanele kokunye ukulandelana okudala ukuguqulwa kwenkulumo yazo.

Izici zokufaka ikhodi zokukhula noma ama-receptors azo:

• I-PDGF: ifaka ikhodi yokukhula kweplatelet ehlotshaniswa ne-glioma (umdlavuza wobuchopho);
  I-Erb-B: ifaka ikhodi yokwamukela i-epidermal factor factor. Ihlotshaniswa ne-glioblastoma (umdlavuza wobuchopho) nomdlavuza webele;
• I-Erb-B2 ibizwa nangokuthi i-HER-2 noma neu: ifaka i-receptor factor factor. Ihambisana nesifuba, indlala yamathe kanye nomdlavuza we-ovari;
• I-RET: ifaka i-receptor factor factor. Ihambisana nomdlavuza wegilo.

I-Genes encoding cytoplasmic relays ezindleleni zokuvuselela:

• I-Ki-ras: ehambisana nomdlavuza wamaphaphu, owesibelethweni, wekoloni nowe-pancreatic;
• I-N-ras: ehambisana ne-leukemia.

Izakhi zofuzo zokufaka umbhalo ezisebenzisa izinhlobo zofuzo ezikhuthaza ukukhula:

• I-C-myc: ehambisana nomdlavuza wegazi kanye nomdlavuza webele, wesisu nowamaphaphu;
• I-N-myc: ihlotshaniswa ne-neuroblastoma (umdlavuza wamaseli ezinzwa) kanye ne-glioblastoma;
• L-myc: ehambisana nomdlavuza wamaphaphu.

Izakhi zofuzo zifaka amanye ama-molecule:

• I-Hcl-2: ifaka amaprotheni ngokuvamile avimba ukuzibulala kwamaseli. Ihambisana nama-lymphomas ama-lymphocyte B;
• UBel-1: obizwa nangokuthi yi-PRAD1. I-Encode Cyclin DXNUMX, isisebenzisi sewashi lomjikelezo weseli. Ihambisana nomdlavuza webele, wekhanda nowentamo;
• I-MDM2: ifaka ikhodi ephikisana neprotheni ekhiqizwa yi-tumor suppressor gene.
• I-P53: ihlotshaniswa nama-sarcomas (izixhumo zomdlavuza wezicubu) kanye neminye imidlavuza.

Amagciwane e-Oncogenic ngamagciwane anekhono lokwenza ukuthi iseli lithelele umdlavuza. U-15% womdlavuza une-etiology yegciwane lesandulela ngculaza kanti lawa mdlavuza wegciwane uyimbangela yamacala amasha alinganiselwa ku-1.5 million ngonyaka nokufa kwabantu abangama-900 ngonyaka emhlabeni jikelele.

Umdlavuza ohlobene negciwane uyinkinga yezempilo yomphakathi:

• i-papillomavirus ihlotshaniswa cishe nama-90% womdlavuza womlomo wesibeletho;
• Ama-75% azo zonke i-hepatocarcinomas axhunyaniswe ne-hepatitis B ne-C virus.

Kunezigaba ezinhlanu zama-oncogenic virus, noma ngabe amagciwane e-RNA noma ama-DNA virus.

Amagciwane e-RNA

• I-Retroviridae (HTVL-1) ikubeka engcupheni ye-T leukemia;
• I-Flaviviridae (igciwane le-hepatitis C) lisengozini ye-hepatocellular carcinoma.

Amagciwane e-DNA

• I-Papovaviridae (i-papillomavirus 16 ne-18) iveza umdlavuza wesibeletho;
• I-Herpesviridae (i-Esptein Barr virus) iveza i-B lymphoma ne-carcinoma;
• I-Herpesviridae (i-herpesvirus yabantu 8) iveza isifo sikaKaposi nama-lymphomas;
• I-Hepadnaviridae (i-virus ye-hepatitis B) isengozini ye-hepatocellular carcinoma.