Studying the effects of low O2 on MM cells: HIF expression and gene regulation caused by hypoxia.

This is some interesting new data that will be published in our forthcoming manuscript. We are awaiting final acceptance from the journal, but we wanted to share some of our initial results. This is a sneak peak of our Fig 1, were we explore the effects of hypoxia on MM cell lines. In Fig1A, we show that generally, most MM cell lines are relatively resistant to hypoxia, with cell death increasing by about 20-40% compared to normal controls. The MM cell lines 8226 and U266 were resistant to hypoxia, while OPM-2 (another cell lines) was much more sensitive. We also studied the regulation of HIF protein under low oxygen conditions. The HIF1- and HIF1-alpha subunits are upregulated by hypoxia (by a process where the protein is stablized) and translocates to the nucleus where it can effect gene transcription. This is shown in Fig 1B, where we compare HIF-alpha regulation in hypoxia-sensitive and hypoxia-resistant cell lines. You can see that low O2 results in upregulation of these subunits in the nucleus. We can also stimulate cells to rapidly increase HIF expression using a hypoxia-mimic (CoCl) as seen in Fig 1C. Next, we show in Fig 1D the expression patterns of 3 or 4 other MM cell lines. In general, HIF1, but not HIF2, was upregulated by hypoxia. This may be an important finding and will be the subject of future studies were we try to define the roles of HIF1 and HIF2 in MM cells. Finallly, we looked at the effects of low oxygen on a number of pro-survival and anti-survival gene expression (Fig 1E). We hope that soon you will be able to read the whole paper!