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. 2024 Sep 6;43:253. doi: 10.1186/s13046-024-03177-7

Fig. 4.

Fig. 4

Suppression of HSF1 activity delays cholangiocarcinogenesis and reduces the proliferation and aggressiveness of AKT/NICD1 mouse lesions. AB Study design. Briefly, wild-type FVB/N mice were subjected to hydrodynamic tail vein injection of either AKT/NICD1/pT3 (control) or AKT/NICD1/HSF1dn plasmids. HSF1dn is the dominant-negative form of the HSF1 transcription factor, whose overexpression effectively inhibits the endogenous HSF1 activity. C While liver lesions from AKT/NICD1 mice consisted of invasive and proliferative (as assessed by positive immunoreactivity for Ki-67) intrahepatic cholangiocarcinomas (upper panels), cystic lesions (denominated cystic adenomas and cystic adenocarcinomas) with low proliferation rate occupied the liver parenchyma of AKT/NICD1/HSF1dn mice. As expected, V5-tagged-HSF1dn staining was observed only in AKT/NICD1/HSF1dn mice. D Liver weight and proliferative activity were significantly higher in AKT/NICD1 mice than in AKT/NICD1/HSF1dn mice. Moreover, the survival curve showed significantly longer survival of AKT/NICD1/HSF1dn mice. Student’s t-test: ***, P < 0.0001; **, P < 0.001. Original magnifications: 40x and 200x; scale bar: 500 μm in 40x and 100 μm in 200x. Abbreviations: H&E, hematoxylin and eosin staining