Læknablaðið : fylgirit - 03.01.2017, Page 70

X V I I I V Í S I N D A R Á Ð S T E F N A H Í
F Y L G I R I T 9 1
70 LÆKNAblaðið/Fylgirit 91 2017/103
Results: Normal RPE cells express MITF and also basal levels of LC3. The
treatment with starvation media and Torin1 treatment resulted in incr-
eased the LC3 protein levels and reduced MITF protein levels. Only the
LC3II protein was detected in RPE cells from MITF mutant whereas wild
type RPE cells showed both LC3I and II.
Conclusion: This study suggests that autophagy is affected in Mitf mutant
mice. This is consistent with in vitro data showing that MITF regulates
expression of genes involved in autophagy.
V 26 The role of the MiT/TFE transcription factor family in autophagy
regulation in melanoma
Ásgeir Ö. Arnþórsson
Eiríkur Steingrímsson’s lab, Biomedical center, UI
aoa12@hi.is
Introduction: Autophagy and lysosomal activity are consider-
ed important for melanoma growth. The MITF transcription factor
is involved in most steps during melanocyte development and has
also been termed a lineage specific oncogene in melanoma. MITF is
related to the TFEB and TFE3 proteins which are involved in regul-
ating expression of lysosomal/autophagy genes through mTORC1
activity and nutrient sensing. All family members can form heter-
odimers and share a similar structure and DNA binding elements.
Methods and data: Our aim was to determine if MITF is also involved
in regulating expression of genes involved in the endolysosmal pathway
in melanoma cells. Using the CRISPR/Cas9 technique we created an
SKMel28 human melanoma cell line lacking MITF. We have used el-
ectron microscopy to characterize endosomes in the mutant cell line.
Results: Our results indicate that knocking out MITF increases the num-
ber of endosomal compartments within these cells. This increase can
be contributed to an increase in TFE3 expression when MITF is absent.
Conclusion: Taken together, our results show that MITF and its close
relative TFE3 regulate autophagy in melanoma and form a regulatory
feedback loop. As both MITF and autophagy have been considered thera-
peutic targets in cancer, identifying this regulatory loop is of great import-
ance.
V 27 The role of MITF in the response to DNA double strand breaks
Drífa H. Guðmundsdóttir1,2, Þorkell Guðjónsson2, Stefán Þ. Sigurðsson2
1Cancer Research Laboratory, UI, 2Faculty of Medicine, UI
dhg1@hi.is
Introduction: The basis of a normal cell function is the integrity of the
genome. When genome instability builds up it can cause uncontrolled cell
proliferation that can develop into malignancies. Cells have developed a
DNA damage response to sense lesions and repair them. DNA double
strand breaks are considered the most cytotoxic of the DNA lesions. Many
proteins play a part in the double strand breaks response and mutations
in these proteins cause a predisposition of developing cancer. It has been
shown that MITF, a well-established transcription factor of melanocytes,
interacts with key factors of the DNA damage response. Here we show
that MITF has a potential role in the double strand break response.
Materials and methods: Double strand breaks were induced using ion-
izing radiation and Doxorubicin. MITF protein levels were measured with
western blotting and immunohistochemistry and confocal imaging. qPCR
was used to measure MITF expression.
Results: As a response to double strand breaks, MITF nuclear intensity
increases in U2OS and SkMel28 cells. Knockdown of MITF triggers
accumulation of DNA damage. And MITF localizes with repair proteins
at sites of double strand breaks.
Conclusion: Many proteins are known for their key roles in the dou-
ble strand break response. Mutations in these proteins can have major
consequences as DNA instability builds up. MITF is a potential partaker
in this response as it shows interaction with some of its best established
proteins. It also accumulates as a response to double strand breaks and is
located at the sites of damage.
V 28 Starfstengdir sjúkdómar tannsmiða. Um heilsu tannsmiða og
aðbúnað á vinnustöðum
Alexander N. Baldursson, Aðalheiður S. Sigurðardóttir
Tannlæknadeild Háskóla Íslands
ass34@hi.is
Inngangur: Markmið rannsóknarinnar var að kanna hvort tannsmiðir á
Íslandi hafi fundið fyrir óþægindum sem þeir tengja beint við vinnu sína
sem tannsmiðir, hvort forvarnir sem geta spornað gegn þessum óþægind-
um séu til staðar á vinnustaðnum og hvort tannsmiðir telji vinnuaðstöðu
sína nægilega útbúna til að stuðla að þeim forvörnum.
Efniviður og aðferðir: Úrtaki í Tannsmiðafélagi Íslands var send-
ur rafrænn spurningarlisti um starfstengda þætti og heilsufar. Not-
uð var megindleg aðferðafræði og unnin lýsandi tölfræði úr gögn-
um með Microsoft Excel og SPSS til að skýra frá niðurstöðum.
Niðurstöður: Svarhlutfall var 52,9% (n=46), þar af karlar (26%,n=12)
og konur (74%,n=34). Flestir voru milli 35-44 ára og meðalaldur 46,6
ár, þriðjungur hafði 0-10 ára starfsaldur. Flestir störfuðu við krónu- og
brúargerð (68%, n=29) eða heilgómagerð (60,9%,n=28). Oftast unnu tve-
ir eða fleiri á vinnustaðnum og í 80% tilfella mátti finna þar allflesta ör-
yggisþætti sem spurt var um. Helstu starfstengdu líkamlegu einkenni
sem þátttakendur upplifðu tengdust stoðkerfi og almennri heilsu.
Ályktun: Mikilvægt er að tannsmiðir beri ábyrgð á eigin heilsufari og fari
reglulega í heilsufarsskoðun, áhersla skal vera lögð á að kanna lungna-
starfssemi, húðsjúkdóma, háls-, nef- eða eyrnasjúkdóma og heyrn. Þessir
þættir eru fyrirbyggjandi og geta dregið úr eða komið í veg fyrir þróun
atvinnusjúkdóma og stuðlað að betri andlegri-, félagslegri- og líkamlegri
líðan. Líkamleg vanlíðan starfsfólks vegna áhættuþátta í umhverfi getur
leitt til starfstengdra sjúkdóma, því ætti vinnuveitandi, í þeim tilfellum
sem við á, að sjá hag sinn í að leggja áherslu á forvarnir, hvetja starfsfólk til
notkunar persónuhlífa og stuðla að heilsueflandi aðgerðum.
V 29 Psychometric Testing of the Iceland Health Care Practitioner
Illness Beliefs Questionnaire among School Nurses
Erla Kolbrún Svavarsdóttir1, Wendy Looman2, Guðný Bergþóra Tryggvadottir3,
Ann Garwick2
1Faculty of Nursing, UI, 2School of Nursing University of Minnesota, 3Faculty of Social and
Human Sciences, UI
eks@hi.is
Background: Beliefs have been found to have an effect on how people deal
with illness. Therefore, knowing health care practitioners’ beliefs about
specific high frequency illnesses are vital when caring for vulnerable
populations such as school age children with chronic illnesses/disorders.
The aim of this study was to develop and psychometrically test the Iceland
Health Care Practitioner Illness Beliefs Questionnaire (ICE-HCP-IBQ) for
school nurses who are working with families of school age children with