Figure 6: Expression of c-myc, hnRNP H, and a-raf isoforms in carcinomas and adjacent normal tissues.
(A) The expression of a-rafshort, a-rafWT, hnRNP H, and c-myc mRNA was assessed in head and neck (HNSCC) tumours (T) and normal adjacent tissues (N) by semi-quantitative RT-PCR. Mapk1 mRNA levels were determined as a loading control. (B) Relative expression of c-myc, hnRNP H and a-raf isoforms in head and neck tissues (left panel) and in colon carcinomas (n=29) and adjacent normal tissues (n=29) (right panel) according to disease state. Shown are boxplots where boxes indicate the median (line) and IQR, whiskers show the range, and asterisks indicate outliers. (C) Scatterplots are used to illustrate the degree of correlation between c-myc/hnRNPH, hnRNP H/a-rafWT, and hnRNPH/a-rafshort relative expression in tumours (red) and normal tissues (blue). (D) Hypothesis and model for hnRNP H-mediated A-Raf isoform selection. In normal cells, low levels of the proto-oncogene c-Myc and the splice factor hnRNP H ensure increased A-Rafshort levels thus keeping proliferation via MAPK signalling in check. Tumour cells show higher expression of both c-Myc and hnRNP H thereby enabling sufficient A-RafWT expression and keeping MST-2 mediated apoptosis in check. Additionally, A-Rafshort is downregulated in tumour cells enabling increased proliferation.