Inhibition of STAT3-interacting protein 1 (STATIP1) promotes STAT3 transcriptional up-regulation and imatinib mesylate resistance in the chronic myeloid leukemia.

BACKGROUND:Signal transducer and activator of transcription 3 is an important transcriptional factor frequently associated with the proliferation and survival of a large number of distinct cancer types. However, the signaling pathways and mechanisms that regulate activation remain to be elucidated. METHODS:In this study we took advantage of existing cellular models for chronic myeloid leukemia resistance, western blot, in vitro signaling, real time PCR, flow cytometry approaches for cell cycle and apoptosis evaluation and siRNA assay in order to investigate the possible relationship between duanyu18133 and CML resistance. RESULTS:Here, we report the characterization of duanyu18133 protein regulation by protein in the leukemia cell line K562, which demonstrates constitutive BCR-ABL TK activity. K562 cells exhibit high levels of phosphorylated duanyu18133 accumulated in the nucleus and enhanced BCR-ABL-dependent duanyu18133 transcriptional activity. Moreover, we demonstrate that is not involved in either BCR-ABL or duanyu18133 signaling but that duanyu1813IP1 is involved in the down-regulation of duanyu18133 transcription levels; K562 cells display increased proliferation and increased levels of the anti-apoptosis duanyu18133 target genes CCND1 and BCL-XL, respectively. Furthermore, we demonstrated that Lucena, an Imatinib (IM)-resistant cell line, exhibits lower duanyu1813IP1 mRNA levels and undergoes apoptosis/cell cycle arrest in response to duanyu18133 inhibition together with IM treatment. We provide evidence that duanyu1813IP1 siRNA could confer therapy resistance in the K562 cells. Moreover, analysis of CML patients showed an inverse expression of STAIP1 and duanyu18133 mRNA levels, ratifying that IM-resistant patients present low duanyu18133 mRNA levels. CONCLUSIONS:Our data suggest that duanyu1813IP1 may be a negative regulator of duanyu18133 and demonstrate its involvement in IM therapy resistance in CML.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}