Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin

Rintasyöpä on johtava naisten syöpäkuolemien aiheuttaja maailmanlaajuisesti. Luun morfogeneettiset proteiinit (BMP) ovat tranformoiva kasvutekijä beta- superperheeseen kuuluvia proteiineja. BMP:den tiedetään olevan osallisina monissa syöpätyypeissä. Rintasyövässä BMP4:llä on merkittäviä vaikutuksia...

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Main Author: Lappeteläinen, Johanna
Other Authors: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylän yliopisto
Format: Master's thesis
Language:fin
Published: 2017
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/56548
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author Lappeteläinen, Johanna
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science University of Jyväskylä Jyväskylän yliopisto
author_facet Lappeteläinen, Johanna Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science University of Jyväskylä Jyväskylän yliopisto Lappeteläinen, Johanna Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science University of Jyväskylä Jyväskylän yliopisto
author_sort Lappeteläinen, Johanna
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description Rintasyöpä on johtava naisten syöpäkuolemien aiheuttaja maailmanlaajuisesti. Luun morfogeneettiset proteiinit (BMP) ovat tranformoiva kasvutekijä beta- superperheeseen kuuluvia proteiineja. BMP:den tiedetään olevan osallisina monissa syöpätyypeissä. Rintasyövässä BMP4:llä on merkittäviä vaikutuksia solukasvuun, liikkuvuuteen ja levinnäisyyteen. Aiempien tutkimusten mukaan BMP4:n on havaittu laskevan solukasvua merkittävästi rintasyöpäsoluilla. Tämän tutkimuksen kohteena oli kaksi BMP4:n kohdegeeniä, ID2 (Inhibitor of DNA binding 2) ja SKIL eli SKI-like proto-onkogeeni. Hypoteesina oli selvittää johtuuko BMP4:n vaikutukset solukasvuun ID2- tai SKIL-geenistä. BT-474 ja T-47D rintasyöpäsoluja käsiteltiin ihmisen rekombinantti proteiini BMP4:lla tai pelkällä kuljettimella ( BMP4:n liuoitusneste). ID2 ja SKIL hiljennettiin RNA häirinnän avulla käyttäen geeneihin kohdennettuja siRNAa: siSKIL, siID2 ja kontrollina lusiferaasigeenin hiljentävä siLUC. Hiljentämisen vaikutuksia solukasvuun määritettiin solulaskuin kahdessa aikapisteessä. Geenien hiljentyminen varmistettiin RT-qPCR:llä. BMP4 laski solukasvua BT-474 ja T-47D soluilla merkittävästi. BMP4:n vaikutukset olivat yhteneväiset ryhmän aiempien tutkimusten kanssa. Solulaskujen perusteella geenien hiljentämisellä ei ollut vaikutusta solukasvuun. Tutkimuksen tarkoituksena oli selvittää ovatko kyseiset geenit osallisena BMP4:n aiheuttamaan solukasvun alenemiseen. Tulokset osoittivat etteivät ID2 tai SKIL ainakaan yksistään ole vastuussa BMP4:n vaikutuksista solukasvuun. Breast cancer is the leading cause of cancer deaths among women worldwide. Bone morphogenetic proteins (BMPs) are a protein family that belongs to transforming growth factor β superfamily. BMPs are involved in many cancer types. In the case of breast cancer BMP4 has a significant influence on cell growth, migration, and invasion. Previous studies have shown that BMP4 decreased cell growth of breast cancer cells significantly. The aim of this study was to examine two BMP4 target genes, Inhibitor of DNA binding 2 (ID2) and SKI-like proto-oncogene (SKIL). The hypothesis was that ID2 and SKIL were involved in the effects of BMP4 on cell growth. Breast cancer cells BT-474 and T-47D were treated with human recombinant BMP4 or vehicle (0,1 % BSA in 4 mM HCl). ID2 and SKIL were silenced by RNA interference using the targeted siRNAs; siSKIL, siID2 and a control was siLUC (luciferase gene). Effects of silencing on cell growth were followed by cell counting in two time points. Gene silencing was confirmed by qPCR. BMP4 decreased the growth of BT-474 and T-47D cells significantly. Effects of BMP4 were consistent with previous studies. Results of cell counting showed that the silencing of the genes did not affect cell growth. In conclusion, the aim was to observe whether the BMP4 target genes were involved in the BMP4 -induced decrease of cell growth in breast cancer cells. The results showed BMP4 decreased cell growth but they also showed that ID2 or SKIL alone does not to affect cell growth.
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Luun\nmorfogeneettiset proteiinit (BMP) ovat tranformoiva kasvutekij\u00e4 beta- superperheeseen\nkuuluvia proteiineja. BMP:den tiedet\u00e4\u00e4n olevan osallisina monissa sy\u00f6p\u00e4tyypeiss\u00e4.\nRintasy\u00f6v\u00e4ss\u00e4 BMP4:ll\u00e4 on merkitt\u00e4vi\u00e4 vaikutuksia solukasvuun, liikkuvuuteen ja\nlevinn\u00e4isyyteen. Aiempien tutkimusten mukaan BMP4:n on havaittu laskevan solukasvua\nmerkitt\u00e4v\u00e4sti rintasy\u00f6p\u00e4soluilla. T\u00e4m\u00e4n tutkimuksen kohteena oli kaksi BMP4:n\nkohdegeeni\u00e4, ID2 (Inhibitor of DNA binding 2) ja SKIL eli SKI-like proto-onkogeeni.\nHypoteesina oli selvitt\u00e4\u00e4 johtuuko BMP4:n vaikutukset solukasvuun ID2- tai SKIL-geenist\u00e4.\nBT-474 ja T-47D rintasy\u00f6p\u00e4soluja k\u00e4siteltiin ihmisen rekombinantti proteiini BMP4:lla tai\npelk\u00e4ll\u00e4 kuljettimella ( BMP4:n liuoitusneste). 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spellingShingle Lappeteläinen, Johanna Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin BMP BMP4 ID2 SKIL Solu- ja molekyylibiologia Cell and molecular biology 4013 rintasyöpä
title Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin
title_full Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin
title_fullStr Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin
title_full_unstemmed Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin
title_short Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin
title_sort luun morfogeneettisen proteiini 4 n kohdegeenien skil ja id2 vaikutukset rintasyöpäsoluihin
title_txtP Luun morfogeneettisen proteiini 4:n kohdegeenien SKIL ja ID2 vaikutukset rintasyöpäsoluihin
topic BMP BMP4 ID2 SKIL Solu- ja molekyylibiologia Cell and molecular biology 4013 rintasyöpä
topic_facet 4013 BMP BMP4 Cell and molecular biology ID2 SKIL Solu- ja molekyylibiologia rintasyöpä
url https://jyx.jyu.fi/handle/123456789/56548 http://www.urn.fi/URN:NBN:fi:jyu-201712274887
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