The Sox6-SOCS3 axis negatively regulates IGF-1 gene transcription. (A) SOCS3 and Sox6 overexpression was accompanied by a strong repression of IGF-1 transcription. (Top panel) Reverse-transcription PCR; (bottom panel) real-time PCR. PCR cycles for IGF-1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) amplifications are indicated below the figure. (B) Diagram showing the known relationships (references are indicated above the connecting lines38,40,41 ) between the genes/pathways studied in the present report. SOCS3 interferes with the EPO/JAK/STAT pathway by binding the EPO receptor (EpoR) and JAK,38 and it interferes with IGF-1 signaling by binding IGF-1R.41 K562 proliferation is sustained by an autocrine IGF-1 signaling loop activated by Bcr/Abl.40 Here, we propose that the SOCS3-mediated inhibition of IGF-1 transcription might be responsible for K562 decreased proliferation and increased apoptosis downstream of Sox6 (solid line). We cannot exclude that Sox6 could also act on IGF-1 through other unknown pathways (dashed line).
