Vincristine-induced expression of P-glycoprotein in MOLM-13 and SKM-1 acute myeloid leukemia cell lines is associated with coexpression of nestin transcript

Abstract

Abstract.Nestin is a class 6 filament protein typically expressed in neural stem/progenitor cells. However, nestin expression has been observed in other tissues during mammalian embryogenesis. In human neural stem/progenitor cells, coexpression of nestin and P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family) was detected. P-gp-mediated drug efflux is the most common molecular cause of multidrug resistance in neoplastic cells. Nestin expression has also been detected in various human solid tumours as well as in the corresponding established cell lines. Interestingly, expression of nestin in different leukemia cells has been recently reported. Here, we show that expression of P-gp is associated with the simultaneous expression of nestin in acute myeloid leukemia cell lines (MOLM-13 and SKM-1) under the selective pressure of vincristine, a substance that may induce P-gp expression in neoplastic cells.

Selection of resistant acute myeloid leukemia SKM-1 and MOLM-13 cells by vincristine-, mitoxantrone- and lenalidomide-induced upregulation of P-glycoprotein activity and downregulation of CD33 cell surface exposure

“…4). The level of P-gp protein in SKM-1 and MOLM-13 cells is so low 407 that it is difficult to detect by western blot using the c219 anti-P-gp 408 antibody (Imrichova et al, 2014). This is consistent with our results Table 1) contain large amounts of P-gp 414 protein (Fig.…”

Overexpression of the ABCB1 drug transporter in acute myeloid leukemia cells is associated with downregulation of latrophilin-1

“…P-gp expression also plays a role in AML cells and represents a real obstacle against effective chemotherapy of this type of leukemia (Broxterman et al 2000;Gao et al 2015). Recently, we described the establishment of a P-gp-positive variant of human AML cells (SKM-1/VCR and MOLM-13/VCR) by selection in medium with stepwise-increasing concentrations of vincristine (Imrichova et al 2014(Imrichova et al , 2015Coculova et al 2016). The expression of P-gp in AML cells was associated with the coexpression of class 6 filament protein nestin, whose expression is typical for neural stem cells and neural progenitor cells (Imrichova et al 2014;Coculova et al 2016), and the downregulation of the plasma membrane expression of AML marker protein CD33 (Imrichova et al 2015).…”

The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin

“…• L1210/R and L1210/T, obtained either by cultivation in stepwise-increasing concentrations of VCR (Polekova et al 1992) or by transfection with a retrovirus encoding human P-gp ; the retrovirus was pHaMDRwt (Addgene product 10957 USA), which contains the full-length P-gp cDNA (Pastan et al 1988); • SKM-1/VCR and SKM-1/LEN, obtained by culturing in media with stepwise-increasing concentrations of VCR (Sigma Aldrich, USA) and LEN (Imrichova et al 2014(Imrichova et al , 2015; • MOLM-13/VCR, obtained by culturing in media with stepwise-increasing concentrations of VCR (Imrichova et al 2014(Imrichova et al , 2015. All variants of L1210 were cultured in RPMI 1640 medium (GE Healthcare) containing 4% fetal bovine serum (Biotech, SR) and 1 μg/ml of gentamicin (Gibco, USA) at 37°C in a humidified atmosphere containing 5% CO 2 .…”

“…• Murine lymphocytic leukemia L1210 (ACC 123); • Human acute myeloid leukemia SKM-1 (ACC 547); • Human acute myeloid leukemia MOLM-13 (ACC 554); • MOLM-13/LEN, obtained by culturing in media with stepwise increasing concentrations of LEN (Celgene, USA) (Imrichova et al 2014(Imrichova et al , 2015) P-gp-positive cell variants:…”