Apoptoza i ne-apoptotičke vrste stanične smrti prilikom tumorigeneze

undergraduate thesis

• Title (english): Apoptosis and non-apoptotic types of cell death during tumorigenesis
• Author: Veronika Buršić
• Mentor: Inga Marijanović (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Višestanični eukariotski organizmi imaju reguliran proces stanične smrti. Ukoliko je
stanična smrt onemogućena ona može biti uzrok nastanka različitih bolesti pa tako i tumora.
Apoptoza ili programirana stanična smrt je proces koji se zasniva na aktivnosti cisteinskih
aspartat-specifičnih proteaza koje nazivamo kaspazama. Osim ovog oblika stanične smrti
poznajemo i druge ne-apoptotičke oblike stanične smrti (autofagija, nekroptoza, senescencija,
anoikis, mitotička katastrofa i drugi) koji se mogu biti prisutni neovisno o apoptozi, ali i ukoliko
je apoptoza iz nekog razloga onemogućena. Jedna od glavnih karakteristika tumorskih stanica
jesu poremećaji u putevima stanične smrti. U ljudi dolazi do nastanka tumora kada geni koji
reguliraju normalnu staničnu diobu (proto-onkogeni i tumor supresorski geni) postanu
disfunkcionalni, aktivirani u krivo vrijeme ili izmijenjeni. Porodica onkogena MYC ključna je
u tumorigenezi i izmijenjena u 70% humanih tumora kada gen MYC ima konstitutivnu
ekspresiju. Proteinski produkti ovog gena igraju ključnu ulogu u progresiji staničnog ciklusa,
apoptozi i staničnoj transformaciji. Članovi porodice proteina Bcl-2 prekomjerno su
eksprimirani u tumorskim stanicama te induciraju transformaciju blokiranjem apoptoze.
Nadalje, visoka ekspresija IAP proteina zabilježena je u raznim slučajevima malignih tumora,
što je takve tumore okarakteriziralo rezistentnima na kemoterapiju i radioterapiju. U većini
slučajeva cilj je eliminirati tumorske stanice reaktivacijom puteva stanične smrti. To možemo
učiniti ciljanjem na anti-apoptozne proteine kao što su Bcl-2 i skupina proteina IAP ili
reaktivacijom p53 odgovora. Načini na koje stanica može umrijeti kao i mehanizmi kojima
ostvaruje nekontroliranu proliferaciju i rezistenciju na staničnu smrt važna su meta u
istraživanju tumora i kreiranju protutumorske terapije.

Abstract (english)

One of the main characteristics of multicellular eukaryotic organisms is that they have
regulated process of cell death. In the cases when cell death is blocked it can trigger many
different diseases as well as tumour formation. Apoptosis or programmed cell death is a process
based on the activity of aspartate-specific cysteine proteases called caspases. Except for
apoptosis, there are several other types of non-apoptotic cell death (autophagy, necroptosis,
senescence, anoikis, mitotic catastrophe and others) which can occur independently of
apoptosis or in cases when apoptosis is blocked. One of the main characteristics of tumour cells
is deregulated cell death. Tumour development in humans is activated when genes responsible
for regulation of cell division (proto-oncogenes and tumour-suppressor genes) become
dysfunctional, activated in a wrong time or modified. MYC family of oncogenes is crucial in
tumorigenesis and it’s modified in 70% of human tumours when this gene has constitutive
expression. Protein products of MYC oncogenes are of high importance in the progression of
cell cycle, apoptosis and tumour transformation. Furthermore, members of the Bcl-2 family of
proteins are overexpressed in tumour cells and induce transformation by blocking apoptosis.
Likewise, overexpression of IAP family members is noticed in different cases of malignant
tumours enabling their resistance to chemotherapy and radiotherapy. In most cases, the aim of
the therapy is to eliminate tumour cells reactivating the cell death pathways. We are able to do
that by targeting anti-apoptotic proteins as Bcl-2 and IAP family members or reactivating p53
response. Pathways regulating cell death, as well as mechanisms of uncontrolled proliferation
and drug resistance are a valuable target for cancer research and anti-tumour therapy design.

• Keywords: stanična smrt; tumorigeneza
• Language: croatian
• URN:NBN: urn:nbn:hr:217:898964
• Study programme: Title: Ecology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-10-29 13:17:52