Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in Drosophila
Figure 4
The Ct switch function represents a cancer prevention mechanism.
(A–M) Adult compound eyes of the respective genotypes are shown. (L) eyeful::ctRNAi; p35 flies show high frequency of long range metastasis (marked by yellow arrowhead), a close-up of which is shown in (M). Eyes of such eyeful::ctRNAi; p35 flies show undifferentiated and overproliferated eye tissue (marked by light blue arrowhead). (N) Quantification of primary and secondary tumor formation in different genetic backgrounds. (O) Relative transcript levels of selected genes involved in cell cycle control, DNA damage response, growth control and epigenetic regulation in eye-antennal discs of 3rd instar larvae of pre-oncogenic control animals (ey::Dl) and animals with reduced Ct activity (ey::Dl;2xctRNAi). (P) Expression of the apoptosis marker Caspase-3 (Casp-3) and the proliferation marker Phosphorylated histone H3 (PH3) in representative 3rd instar eye-antennal discs of ey::Dl and ey::Dl;2xctRNAi animals. An increase in Casp-3 and PH3 positive cells is seen in the area below the dashed, yellow line highlighting the morphogenetic furrow. (Q) Top panel: representative pictures of eyes from ey::Dl;PI3KRNAi and ey::Dl;2xctRNAi;PI3KRNAi animals. Bottom panel: quantification of tumorous eye growth, secondary tumor growth and “small eye” phenotype in ey::Dl;2xctRNAi and ey::Dl;2xctRNAi;PI3KRNAi and ey::Dl;PI3KRNAi animals.