Table 5 |
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|
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. |
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|
Gene symbol |
Gene name |
Probes upregulated |
Additional information |
Apoptotic function |
|
|
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|
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 |
|
|
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|
Daigeler et al. BMC Cancer 2008 8:313 doi:10.1186/1471-2407-8-313 |
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