Table 5 Summary of genes beyond the ones already mentioned in the text that were found to be up-regulated by doxorubicin treatment in more than 50% of the probes.
Gene symbol | Gene name | Probes upregulated | Additional information | Apoptotic function |
|---|---|---|---|---|
PAWR | PRKC (protein kinase C) apoptosis WT1 (Wilms tumor gene) regulator protein | 11 | STS with high WT1 mRNA expression levels have poorer outcome than those with low levels [89, 90]. Ecteinascidin that has been shown to be effective against STS also increases expression of PAWR [92]. PAWR inhibits the PKC (atypical protein kinase)-NF-(kappa)B (nuclear factor-(kappa)B)-XIAP pathway [91]. | proapoptotic |
TNFAIP3 | tumor necrosis factor, alpha-induced protein 3 | 11 | TNFAIP3 down-regulates the TNF-α-induced NFκB signalling pathway [93, 94]. | antiapoptotic |
NFKBIA | nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha | 10 | The doxorubicin analogon DA-125 reduces proliferation in HT1080 fibrosarcoma cells through a NFKB dependent pathway [96, 97]. MDM2 (upregulated in 9 samples in our series) is overexpressed in several liposarcoma subtypes [58] and increases NFKB activity in a p53 dependent manner and thereby leads to doxorubicin resistance [98]. | proapoptotic/antiapoptotic |
IER3 | immediate early response 3 | 10 | IER3 function is increased by p53, that is induced by doxorubicin. IER3 is involved in cell cycle arrest and programmed cell death [99, 100]. | proapoptotic |
PSEN1 | presenilin 1 | 10 | Effects are mediated via Bcl-2 interaction [101]. | proapoptotic |
RIPK2 | receptor-interacting serine-threonine kinase 2 | 10 | RIPK2 is cell death inducing and NFKB activating, via caspase 1 activation [102, 103]. | proapoptotic |
PEA15 | phosphoprotein enriched in astrocytes 15 | 10 | RPEA15 is regulating caspase-3 function in epidermal cells [104], but has not yet been associated with doxorubicin treatment or apoptosis in sarcoma cells. | antiapoptotic |
BCL2A1 | BCL2 (B-cell CLL/lymphoma 2)-related protein A1 | 10 | antiapoptotic | |
NGFB | nerve growth factor, beta polypeptide | 10 | NGF reduces apoptosis induced by chemotherapeutics in sarcoma cells [109]. | antiapoptotic |
BIRC3 | baculoviral IAP repeat-containing 3 | 10 | BIRC3 is associated with chemotherapy resistance in Ewing sarcoma, rhabdomyosarcoma [110] and prostatic cancer [111]. | antiapoptotic |
CD44 | cell surface glycoprotein CD44 | 10 | CD44 is a proapoptotic factor in FAS mediated apoptosis in sarcoma cells [112], but is also connected to cancer drug resistance [113]. CD44 has successfully been used as a target for liposomal encapsuled doxorubicin [114]. | proapoptotic/antiapoptotic |