Table 1 Differential gene expression in parental HCT116 and 5-FU-resistant cell lines: DNA damage response/repair, cell cycle, and apoptosis regulatory pathways.
Gene symbol | parent al 8 hr 5 FUa | parenta l 24 hr 5 FU a | Contin B 8 hr 5 FU a | Contin B 24 hr 5 FU a | Contin D 8 hr 5 FU a | Contin D 24 hr 5 FU a | altered in ContinB as a result of resistance development b | altered in ContinD as a result of resistance development b | Regulatory pathway/function |
|---|---|---|---|---|---|---|---|---|---|
| Â | Â | Â | Â | Â | Â | Â | Â | Â | DNA damage response/DNA repair |
ATF3 | 2.1 | 3.1 | 1.5 | 2.3 | 1.8 | 2.8 | -0.7 | -1.2 | protective response of human cells to ionizing radiation |
GADD34 | 0.9 | 1.4 | 0.9 | 1.3 | 0.8 | 1.5 | -0.1 | -0.2 | cellular response to stress and DNA damage stressful growth arrest conditions, treatment with DNA-damaging |
GADD45A | 2.3 | 2.9 | 2.8 | 3.1 | 1.5 | 2.1 | -1.1 | -0.3 | agents |
MMS2 | 0.3 | 0.7 | 0.2 | 0.6 | -0.1 | -0.1 | na | na | cellular response to stress; regulation of DNA repair |
MSH2 | -1.0 | -1.1 | -1.2 | -0.7 | -0.2 | -0.8 | -0.3 | 0.8 | mismatch repair |
PCNA | 1.1 | 2.6 | 0.9 | 2.2 | 0.6 | 1.3 | 0.8 | 0.8 | involved in DNA replication and repair |
RAD23A | -0.2 | -0.4 | -1.6 | -0.5 | -0.1 | 0.1 | na | na | nucleotide excision repair |
TP53 | -0.8 | -1.0 | 0.0 | -0.9 | 0.0 | -0.5 | 0.5 | 0.4 | DNA damage response, negative regulator of cell growth |
TP53I3 | -0.7 | 2.3 | 0.7 | 2.5 | 0.4 | 2.5 | na | na | cellular response to oxidative stresses and irradiation |
XPC | 0.0 | 0.4 | 1.3 | 0.8 | 0.2 | 0.5 | -0.6 | -0.4 | nucleotide excision repair |
| Â | Â | Â | Â | Â | Â | Â | Â | Â | Cell cycle/cell proliferation |
AREG | 0.2 | 1.9 | 0.8 | 3.1 | -0.1 | 1.8 | -2.2 | -2.1 | positive regulator of cell growth; inhibits apoptosis together with IGF1 |
BUB1 | -1.3 | -1.1 | -0.6 | -0.3 | -0.5 | -0.9 | 0.4 | 0.6 | spindle checkpoint function |
BUB1B | -1.4 | -2.5 | -0.9 | -1.8 | -0.9 | -1.4 | 0.6 | 0.6 | spindle checkpoint function |
CCNB1 | -0.3 | -0.5 | -0.5 | -0.4 | -0.5 | -1.8 | na | na | regulates G2M cell cycle transition |
CCNB2 | -0.7 | -1.1 | -0.7 | -0.7 | -0.4 | -1.6 | 0.0 | 0.5 | regulates G2M cell cycle transition |
CCNC | -1.0 | -1.9 | -2.1 | -2.0 | -0.4 | -0.5 | -0.4 | -0.3 | involved in G1 cell cycle regulation |
CCND3 | 0.7 | 1.6 | 0.9 | 2.4 | 0.4 | 1.0 | 1.7 | 0.1 | regulates G1/S cell cycle transition |
CCNG1 | -1.8 | -1.1 | -0.4 | -1.3 | -0.3 | -0.5 | -1.4 | -0.3 | growth inhibitory activity linked to ARF-p53 and pRb pathways. |
CDC25B | -1.6 | -1.4 | -0.9 | -1.2 | -0.3 | -0.6 | 0.2 | -0.7 | dephosphorylates CDC2 to allow progression to mitosis |
CDC6 | 0.7 | 1.1 | -0.6 | 0.0 | 0.2 | 0.2 | 0.8 | 1.0 | regulator at early steps of DNA replication |
CDCA5 | 0.2 | 1.4 | -0.1 | 0.5 | 0.2 | 0.2 | na | na | G1/S transition of cell cycle |
CDKN1A | 2.4 | 3.1 | 2.8 | 3.6 | 1.9 | 3.0 | -0.5 | -1.1 | negative regulator of cell cycle progression at G1 |
CHC1 | -1.5 | -0.2 | -1.4 | -1.1 | -0.4 | -0.2 | 1.8 | 0.7 | regulator of chromosome condensation |
GTF2B | -0.7 | -0.4 | -1.1 | -1.3 | -0.2 | 0.2 | -0.8 | -0.1 | regulation of transcription, DNA-dependent |
H3F3B | -0.7 | -0.6 | -1.9 | -1.1 | -0.1 | 0.0 | -0.1 | -0.1 | chromosome organization and biogenesis; nucleosome assembly |
IRF6 | -0.3 | 0.5 | -0.6 | 0.1 | 0.0 | 1.2 | na | na | regulation of transcription, DNA-dependent |
LIPH | 0.2 | -1.2 | -0.5 | -0.4 | 0.0 | 0.0 | na | na | stimulation of cell proliferation and motility |
MCM3 | -0.6 | -1.5 | -0.4 | -2.1 | 0.0 | -1.9 | 1.0 | 0.8 | initiation of genome replication; formation of replication forks |
MKI67 | -0.8 | -1.2 | 0.0 | -0.4 | -0.1 | -0.4 | 0.8 | 0.9 | antigen identified by monoclonal antibody Ki-67; cell proliferation |
MYC | -0.3 | -1.2 | -1.1 | -1.9 | -0.6 | -0.2 | -0.3 | -0.5 | dual signaling for cell growth and cell death |
NAP1L1 | -0.3 | -0.8 | -0.9 | -1.9 | -0.4 | -0.7 | na | na | DNA replication; positive regulation of cell proliferation |
NBL1 | -1.1 | -1.3 | -0.7 | -0.5 | 0.0 | -0.1 | na | na | transcription factor; negative regulator of cell cycle |
NDEL1 | -0.6 | -0.3 | -1.5 | -1.1 | -0.3 | 0.0 | 0.3 | -0.1 | thiol-activated peptidase phosphorylated in M phase of the cell cycle |
NEK1 | -0.7 | -1.2 | -0.2 | 0.0 | -0.1 | -0.5 | na | na | DNA damage response pathway at the G2/M transition |
NEK4 | -1.0 | -1.2 | -0.6 | -0.8 | -0.5 | -1.2 | na | na | involved in mitosis |
NEK9 | -1.2 | -1.1 | nd | -0.1 | -0.2 | -0.4 | na | na | binds Ran GTPase and regulates mitotic progression |
PARD3 | -0.8 | 0.3 | -0.6 | -1.5 | -0.4 | -0.1 | nd | nd | asymmetric cell division; establishment/maintenance of cell polarity |
PDAP1 | 0.2 | -1.3 | 0.5 | -0.3 | 0.2 | -0.5 | 0.9 | 0.8 | cell proliferation; signal transduction |
PDXP | -0.3 | -1.3 | 0.4 | -0.3 | 0.1 | -0.5 | na | na | maintaining biochemical homeostasis required for proper spindle assembly/function; regulates G2M |
PLK | -2.1 | -2.3 | -1.8 | -2.8 | -0.5 | -1.6 | 1.5 | 0.7 | progression |
PPP2CB | 0.8 | 1.7 | 1.0 | 2.2 | 0.2 | 1.1 | 0.1 | 0.0 | negative regulator of cell growth and division |
PVT1 | -1.4 | -0.7 | 0.6 | 0.4 | 0.1 | 0.4 | na | na | MYC activator |
RAN | -0.6 | -0.8 | -1.2 | -1.6 | 0.0 | -0.3 | 0.0 | 0.2 | translocation of RNA and proteins through nuclear pore complex |
RARRES2 | -1.6 | -0.9 | -0.1 | -0.6 | -0.1 | -0.1 | nd | nd | growth inhibitory and cell differentiation activities |
RFP | -0.6 | -0.4 | -1.0 | -1.1 | -0.1 | 0.2 | na | na | cell proliferation; regulation of transcription, DNA-dependent |
RNF4 | -0.2 | -1.1 | 0.1 | -0.4 | -0.1 | 0.1 | 0.3 | 0.2 | transcription regulator; inhibits activity of TRPS1 |
RRM2 | 0.9 | 1.4 | 0.9 | 1.0 | 0.4 | 0.1 | 0.4 | 0.8 | catalyzes formation of deoxyribonucleotides from ribonucleotides |
RUNX3 | -0.7 | -0.8 | -0.6 | -1.3 | -0.1 | 0.0 | 0.1 | -0.3 | cell proliferation; regulation of transcription, DNA-dependent |
STK6 | -2.1 | -1.5 | -1.1 | -1.4 | -0.8 | -2.1 | 1.0 | 0.8 | microtubule formation at spindle pole during chromosome segregation |
TIMP1 | 0.1 | -0.7 | 0.4 | -0.3 | -0.3 | -1.4 | -0.5 | -0.5 | positive regulation of cell proliferation |
TOP1 | -0.9 | -1.4 | -1.8 | -0.1 | -0.4 | -0.1 | -0.4 | -0.4 | control of DNA topology during transcription |
YWHAE | 0.4 | -1.2 | 0.4 | -0.2 | -0.1 | -0.3 | -1.2 | -0.6 | member of 14-3-3 family of proteins which mediate signal transduction |
| Â | Â | Â | Â | Â | Â | Â | Â | Â | Apoptosis |
AVEN | 0.2 | 1.5 | 1.0 | 1.8 | 0.1 | 1.0 | 0.8 | -0.2 | inhibits Apaf-1-mediated caspase activation |
BAK1 | -0.5 | -0.8 | -0.2 | -0.6 | -0.2 | -0.1 | 0.7 | -0.2 | apoptosis promoter |
BAX | na | na | na | na | na | na | 0.5 | -0.3 | apoptosis promoter |
BCL2 | nd | nd | nd | nd | nd | nd | nd | nd | apoptosis inhibitor |
BIRC5 | -0.2 | -1.2 | nd | 0.0 | -0.1 | -0.3 | 1.2 | 0.7 | apoptosis inhibitor |
BNIP3 | na | na | na | na | na | na | -1.0 | -0.1 | apoptosis promoter |
BNIP3L | -1.3 | -2.0 | nd | -2.0 | -1.4 | -1.0 | -2.7 | -0.5 | apoptosis promoter |
CASP3 | 0.0 | -0.5 | -1.7 | -1.2 | -0.3 | -0.1 | 0.0 | 0.1 | apoptosis promoter |
FAS | 2.1 | 3.8 | 2.9 | 3.3 | 1.8 | 2.2 | 0.2 | 0.2 | apoptosis promoter |
IRAK1 | -0.7 | -0.4 | -0.4 | -0.3 | 0.1 | -0.1 | 1.6 | 0.1 | apoptosis inhibitor |
MALT1 | na | na | na | na | na | na | 1.5 | 0.8 | apoptosis inhibitor |
SERPINB2 | 1.1 | 2.5 | 0.2 | 1.7 | 0.6 | 1.3 | nd | nd | inhibits TNF-alpha-induced apoptosis |
TNFRSF6B | na | na | na | na | na | na | -2.7 | -2.0 | apoptosis inhibitor |