Proteomic analysis of hepatic tumor in Hras12V transgenic mice
Male prevalence is an outstanding characteristic of hepatocellular carcinoma(HCC),and the underlying mechanisms for this have remained largely unknown.In the present study,Hras12V transgenic mice,in which hepatocyte-specific expression of the ras oncogene induces male-biased hepatic tumorigenesis,were studied,and altered proteins were detected by two-dimensional fluorescence difference gel electrophoresis(2D-DIGE).Protein samples from hepatic tumor tissues(T)and peri-tumor tissues(P)of transgenic males and females and the corresponding normal liver tissues(Wt)of non-transgenic males and females were subjected to pairwise comparisons based on proteomic analysis.Among 2381 auto-detected protein spots,more than 1600 were differentially expressed based on a pairwise comparison(|ratio| >= 1.5,p <= 0.05).Of these,180 spots were randomly selected for matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry(MALDI-TOF/TOF MS)identification; finally,89 distinct proteins were obtained.Among these 89 proteins,7 and 50 proteins were further validated by Western blotting and literature investigation,respectively.Intriguingly,compared to Wt,the altered proteins were relatively concentrated in T in transgenic females but in P in transgenic males.Consistently,the levels of p-ERK and p-mTOR were significantly higher in the T of females compared to that of males.The pathway enrichment assay showed that 5 pathways in males but only 1 in females were significantly altered in terms of the up-regulated proteins in T compared to Wt.These data indicate that female hepatocytes are disturbed by oncogenes with great difficulty,whereas male hepatoctyes readily do so.In addition,33 proteins were genderdependently altered in hepatic tumorigenesis.Moreover,4%DNA packaging and 4%homeostasis-related functional proteins were found in females but not in males,and more nucleus proteins were found in females(8%)than in males(3%).In conclusion,the proteomic data and comparative analysis presented here offer crucial clues for elucidating the mechanisms that underlie the male prevalence in HCC.
Hepatic tumor Ras oncogene Gender-dependent Proteomics Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE)
Zhuona Rong Tingting Fan Huiling Li Juan Li Fujin Wang Jingyu Wang Aiguo Wang
Laboratory animal center,Dalian Medical University,Dalian,Liaoning 116000,P.R.China
国内会议
呼和浩特
英文
285-295
2017-09-12（万方平台首次上网日期，不代表论文的发表时间）