Becker, Marco

English

Basal cell carcinoma (BCC) belongs to the group of non-melanoma skin
cancers and is the most commonly diagnosed cancer in fair-skinned
individuals. In the majority of BCC the tumor suppressor gene patched1
(PTCH) is mutated resulting in aberrant hedgehog (HH) signaling. Analysis of
human and murine BCC shows that the putative tumor suppressor Wnt
inhibitory factor 1 (Wif1) is highly expressed by this tumor entity. However,
malignant forms of skin cancer, i.e. squamous cell carcinomas and
melanomas, also express Wif1. Thus, the objective of this thesis was to
analyze the role of Wif1 in BCC by Wif1 overexpression in the BCC cell line
ASZ001 and by Wif1 depletion in the BCC mouse model
Ptch flox/flox CreERT2 T/-.
Indeed, tumor-intrinsic Wif1 overexpression in ASZ001 significantly inhibits
tumor growth in nude mice. The Wif1-mediated tumor suppression was not
due to diminished vascularization or alterations in canonical Wnt, Hh or
PI3K/Akt signaling activity. It also was not due to induction of differentiation
or apoptosis. However, we found that Wif1-expressing tumors were
characterized by a decrease in Ki67 positive cells which was accompanied
by phosphorylation of PKC and Erk1 along with moderately increased
deposition of collagens. Vice versa, BCC growth is enhanced in
Ptch-knockout mice on a Wif1-deficient background due to an increase in
proliferation. Together, the data suggest that Wif1 is both necessary and
sufficient to restrict BCC growth and may be one of the factors that are
responsible for the very low metastatic potential of this tumor entity

Georg-August-University Göttingen

Wif1 Inhibits the Growth of Basal Cell Carcinoma

https://ediss.uni-goettingen.de/bitstream/11858/00-1735-0000-0028-867F-F/1/Becker%20M%202015%20Diss%20fertig%20jetzt%20auch%20mit%20seitenzahlen.pdf

Wif1 Inhibits the Growth of Basal Cell Carcinoma

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Georg-August-University Göttingen