Background
Methods
Mice
Ovariectomy
Mouse Genome CGH Microarrays
Chromosomal Interval | Base Pairs | RM Length | Cytobands | Total Probes | Genes | Probe Density (-RM) |
---|---|---|---|---|---|---|
Chr2:130057657-134054840 | 3,997,184 | 1,593,942 | qF1-qF2 | 4,393 | 97 | 547 |
Chr3:82669962-85356557 | 2,686,596 | 900,443 | qE3-qF1 | 3,263 | 24 | 547 |
Chr11:42126777-46489372 | 4,362,596 | 1,560,848 | qA5-qB1.1 | 5,120 | 49 | 547 |
Chr11:101602336-121653288 | 20,050,953 | 6,694,702 | qD-qE2 | 24,413 | 584 | 547 |
Chr17:71771954-72520788 | 748,835 | 344,281 | qE2 | 740 | 7 | 547 |
Totals
|
31,846,164
|
11,094,216
|
37,929
|
671
| ||
Chr7:1-141,766,352 | 141,766,352 | 58,864,541 | 2,900 | 28,587 | ||
Chr8:1-127,874,053 | 127,874,053 | 48,159,999 | 2,090 | 38,141 | ||
Print Controls | 1,370 | |||||
Totals
|
44,289
|
Gene expression
Results
MINs are heterogeneous
MIN-O line | Major histological characteristics of MIN-Os* | Metastasis Index* | ER status of MIN-Os |
---|---|---|---|
4w-4 | Solid chords & nests | 0 | Negative or cytoplasmic |
4w-11 | Microacini & organized cysts | 0.63 | Mostly cytoplasmic |
8w-B | Dysplastic cysts. Better differentiated. Microacinar structures. | 0 | Nuclear (+++) |
8w-D | Prominent and distinct microacinar patterns. Organized cysts. Patches of eosinophilic microacini. | 0.47 | Nuclear (+) |
Ovarian hormone sensitivity of MIN-Os
MIN-O line | MIN-O size at 5-weeks posttransplantation | Tumor latency (in weeks) | |||||
---|---|---|---|---|---|---|---|
Ovx | |||||||
Control %FPF (n) | % FPF (n) | relative to control | p-value | Control TE50
| Ovx TE50
| p-value | |
4w-4 | 55.00 ± 10.00 (4) | 24.29 ± 9.76 (7) | 0.44 |
0.0008
| 10.1 | >10.1 | 0.113 |
4w-11 | 37.50 ± 17.08 (4) | 15.00 ± 18.17 (6) | 0.40 | 0.08 | 10.2 | 12.1 | 0.118 |
8w-B* | 67.50 ± 12.58 (4) | 22.86 ± 7.56 (7) | 0.34 |
<0.0001
| 4.9 | 11.1 |
0.002
|
8w-D | 60.00 ± 0.00 (4) | 10.71 ± 4.50 (7) | 0.18 |
<0.0001
| 8.15 | 12.1 |
0.017
|
CGH analysis
Expression changes associated with tumorigenesis
Probe Set ID | Gene Title | Gene Symbol | FC in tumors | GO biological function |
---|---|---|---|---|
99104_at | adiponectin, C1Q and collagen domain containing | Adipoq | -21.75 | Lipid metabolism, Organic acid metabolism |
99671_at | adipsin | Adn | -35.98 | |
98924_at | ADP-ribosyltransferase 3 | Art3 | -2.55 | |
92537_g_at | adrenergic receptor, beta 3 | Adrb3 | -2.88 | |
102327_at | amine oxidase, copper containing 3 | Aoc3 | -3.66 | Cell adhesion |
96785_at | ankyrin repeat domain 47 | Ankrd47 | -2.04 | |
104761_at | anthrax toxin receptor 2 | Antxr2 | -1.60 | |
160375_at | carbonic anhydrase 3 | Car3 | -20.83 | |
101539_f_at | carboxylesterase 3 | Ces3 | -4.06 | Lipid metabolism, Organic acid metabolism |
102016_at | cell death-inducing DFFA-like effector c | Cidec | -4.79 | |
95415_f_at | complement component 1, r subcomponent | C1r | -2.64 | |
92224_at | C-type lectin domain family 3, member b | Clec3b | -5.87 | |
96346_at | cysteine dioxygenase 1, cytosolic | Cdo1 | -9.76 | Organic acid metabolism |
93996_at | cytochrome P450, family 2, subfamily e, polypeptide 1 | Cyp2e1 | -3.54 | |
96742_at | dermatopontin | Dpt | -5.06 | Cell adhesion |
103031_g_at | dynamin 1 | Dnm1 | -2.21 | |
92535_at | early B-cell factor 1 | Ebf1 | -1.81 | |
100567_at | fatty acid binding protein 4, adipocyte | Fabp4 | -2.31 | |
92441_at | fibroblast activation protein | Fap | -2.27 | |
101991_at | flavin containing monooxygenase 1 | Fmo1 | -3.20 | |
93040_at | FXYD domain-containing ion transport regulator 1 | Fxyd1 | -2.69 | |
93750_at | gelsolin | Gsn | -5.43 | |
102373_at | glutamyl aminopeptidase | Enpep | -2.86 | |
99108_s_at | growth hormone receptor | Ghr | -1.99 | |
92833_at | histidine ammonia lyase | Hal | -2.25 | Organic acid metabolism |
95546_g_at | insulin-like growth factor 1 | Igf1 | -2.07 | |
103904_at | insulin-like growth factor binding protein 6 | Igfbp6 | -4.34 | |
92366_at | laminin, alpha 2 | Lama2 | -3.25 | Cell adhesion |
103083_at | lipase, hormone sensitive | Lipe | -2.46 | Lipid metabolism |
160083_at/95611_at | lipoprotein lipase | Lpl | -5.18 | Lipid metabolism |
93353_at | lumican | Lum | -9.33 | |
97520_s_at | neuronatin | Nnat | -5.92 | |
100120_at | nidogen 1 | Nid1 | -2.19 | Cell adhesion |
160481_at | phosphoenolpyruvate carboxykinase 1, cytosolic | Pck1 | -2.61 | Lipid metabolism, Organic acid metabolism |
102763_at | plasma membrane associated protein, S3-12 | MGI:1929709 | -8.13 | |
93826_at | protein phosphatase 2, regulatory subunit B (B56), alpha isoform | Ppp2r5a | -1.43 | |
102366_at | resistin | Retn | -10.89 | |
97835_at | retinoic acid receptor responder (tazarotene induced) 2 | Rarres2 | -6.19 | |
96047_at | retinol binding protein 4, plasma | Rbp4 | -4.08 | |
104445_at | RIKEN cDNA 4631408O11 gene | 4631408O11Rik | -5.20 | |
101861_at | sarcoglycan, epsilon | Sgce | -1.62 | |
102707_f_at | serine (or cysteine) peptidase inhibitor, clade A, member 3C | Serpina3c | -1.94 | |
97429_at | SNF related kinase | Snrk | -1.65 | |
92582_at | solute carrier family 1 (neutral amino acid transporter), member 5 | Slc1a5 | -1.94 | |
160320_at | sorbin and SH3 domain containing 1 | Sorbs1 | -2.74 | Cell adhesion |
94056_at/94057_g_at | stearoyl-Coenzyme A desaturase 1 | Scd1 | -2.76 | Lipid metabolism, Organic acid metabolism |
103087_at | sulfotransferase family 1A, phenol-preferring, member 1 | Sult1a1 | -1.68 | Lipid metabolism |
103568_at | sushi-repeat-containing protein | Srpx | -2.84 | |
104280_at | synuclein, gamma | Sncg | -4.63 | |
102916_s_at/161907_s_at | tenascin XB | Tnxb | -4.73 | Cell adhesion |
160547_s_at | thioredoxin interacting protein | Txnip | -2.83 | |
99052_at | zinc finger homeobox 1a | Zfhx1a | -1.63 |
Molecular changes associated with each MIN-O line
Recurring genomic aberration by MIN-O lines
# of probes | ||||
---|---|---|---|---|
p-value | increased | decreased | total probes | |
Chr 2 | <0.01 | 60 | 5 | 871 |
<0.05 | 143 | 15 |
# of probes | ||||
---|---|---|---|---|
p-value | increased | decreased | total probes | |
Chr 1 | <0.01 | 78 | 11 | 652 |
<0.05 | 217 | 24 | ||
Chr 10 | <0.01 | 61 | 4 | 481 |
<0.05 | 139 | 14 | ||
Chr 11 | <0.01 | 121 | 11 | 957 |
<0.05 | 255 | 36 |
Zoom-in arrays
Genes | U74Av2 probe ID | lower expression in 8w-D MIN-Os* |
---|---|---|
Hspa12b | ||
1700037H04Rik | 97210_at | x |
Spef1/4931426K16Rik | 93475_at | x |
Cenpb | 99486_at | x |
cdc25b | 99012_at | |
2310035K24Rik | 96819_at | |
D430028G21Rik | ||
Pank2 | ||
Rnf24 | 97200_f_at | x |
Smox | ||
Adra1d | ||
1600014E20Rik | 161097_at | |
Prnp | 100606_at | x |
Prnd | ||
Rassf2 | 94771_at | |
Slc23a2 | 104267_at | x |
Genes | U74Av2 probe ID | higher expression in 5189MINO** |
---|---|---|
Pttg1 | 101026_at | x |
D11Ertd730e | 160772_I_at | x |
161428_at | x | |
C1qtnf2 | ||
Fabp6 | 99977_at | x |
Ttc1 | 96921_at | x |
161887_r_at | x | |
Adra1b | 92340_at | x |
Il12b | 100779_at | x |
Ublcp1 | 94865_at | x |
3732413l11Rik | 96104_at | x |
Ebf1 | 92535_at | x |
Gene expression associated with each MIN-O line
Name | GO ID | Corrected P-value |
---|---|---|
Highly significant GO functions
| ||
DNA-dependent DNA replication | GO:0006261 | 0.00E+00 |
organic acid biosynthesis | GO:0016053 | 0.00E+00 |
chromatin assembly or disassembly | GO:0006333 | 0.00E+00 |
nucleosome assembly | GO:0006334 | 0.00E+00 |
regulation of cyclin dependent protein kinase activity | GO:0000079 | 2.68E-02 |
Name | GO ID | Corrected P-value |
---|---|---|
I-kappB/NF-kappaB
| ||
regulation of I-kappaB kinase/NF-kappaB cascade | GO:0043122 | 0.00E+00 |
positive regulation of I-kappaB kinase/NF-kappaB cascade | GO:0043123 | 0.00E+00 |
I-kappaB kinase/NF-kappaB cascade | GO:0007249 | 0.00E+00 |
apoptotic program
| ||
apoptotic program | GO:0008632 | 0.00E+00 |
Immune response
| ||
lymphocyte differentiation | GO:0030098 | 7.04E-03 |
antigen presentation, exogenous antigen | GO:0019884 | 1.59E-02 |
xenobiotic metabolism | GO:0006805 | 2.02E-02 |
T-cell activation | GO:0042110 | 2.72E-02 |
response to xenobiotic stimulus | GO:0009410 | 2.68E-02 |
T-cell differentiation | GO:0030217 | 2.71E-02 |
response to bacteria | GO:0009617 | 2.87E-02 |
regulation of immune response | GO:0050776 | 3.35E-02 |
defense response to bacteria | GO:0042742 | 3.87E-02 |
antigen presentation | GO:0019882 | 4.21E-02 |
Reponse to radiation/UV
| ||
response to radiation | GO:0009314 | 6.37E-03 |
phototransduction | GO:0007602 | 1.53E-02 |
detection of light | GO:0009583 | 1.91E-02 |
response to light | GO:0009416 | 2.79E-02 |
Name | GO ID | Corrected P-value |
---|---|---|
Spindle/Microtubule
| ||
mitotic spindle organization and biogenesis | GO:0007052 | 0.00E+00 |
spindle organization and biogenesis | GO:0007051 | 0.00E+00 |
microtubule cytoskeleton organization and biogenesis | GO:0000226 | 0.00E+00 |
microtubule-based movement | GO:0007018 | 4.70E-07 |
chromosome segregation | GO:0007059 | 4.32E-03 |
microtubule polymerization | GO:0046785 | 1.59E-02 |
microtubule polymerization or depolymerization | GO:0031109 | 1.97E-02 |
M phase specific microtubule process | GO:0000072 | 3.32E-02 |
Cell cycle
| ||
regulation of mitosis | GO:0007088 | 0.00E+00 |
cell cycle checkpoint | GO:0000075 | 0.00E+00 |
interphase of mitotic cell cycle | GO:0051329 | 0.00E+00 |
G1/S transition of mitotic cell cycle | GO:0000082 | 0.00E+00 |
negative regulation of cell cycle | GO:0045786 | 6.08E-03 |
G2/M transition of mitotic cell cycle | GO:0000086 | 1.29E-02 |
mitotic checkpoint | GO:0007093 | 1.28E-02 |
regulation of cyclin dependent protein kinase activity | GO:0000079 | 1.25E-02 |
G1 phase of mitotic cell cycle | GO:0000080 | 1.41E-02 |
traversing start control point of mitotic cell cycle | GO:0007089 | 1.67E-02 |
cell cycle arrest | GO:0007050 | 1.67E-02 |
mitotic anaphase | GO:0000090 | 2.63E-02 |
anaphase | GO:0051322 | 2.72E-02 |
prophase | GO:0051324 | 2.81E-02 |
Angiogenesis
| ||
blood vessel morphogenesis | GO:0048514 | 6.37E-03 |
angiogenesis | GO:0001525 | 1.01E-02 |
blood vessel development | GO:0001568 | 9.73E-03 |
Steroid
| ||
steroid biosynthesis | GO:0006694 | 3.45E-02 |
Name | GO ID | Corrected P-value |
---|---|---|
Response to radiation/UV
| ||
phototransduction | GO:0007602 | 0.00E+00 |
detection of light | GO:0009583 | 0.00E+00 |
response to radiation | GO:0009314 | 0.00E+00 |
response to light | GO:0009416 | 0.00E+00 |
response to UV | GO:0009411 | 2.88E-02 |
Apoptosis
| ||
apoptotic program | GO:0008632 | 0.00E+00 |
Immune response
| ||
complement activation, classical pathway | GO:0006958 | 9.56E-03 |
positive regulation of immune response | GO:0050778 | 1.15E-02 |
regulation of immune response | GO:0050776 | 1.36E-02 |
T-cell activation | GO:0042110 | 2.23E-02 |
antigen processing | GO:0030333 | 2.25E-02 |
cellular defense response (sensu Vertebrata) | GO:0016066 | 2.32E-02 |
antimicrobial humoral response | GO:0019730 | 2.58E-02 |
positive regulation of lymphocyte activation | GO:0051251 | 2.60E-02 |
xenobiotic metabolism | GO:0006805 | 2.58E-02 |
symbiotic interaction between host and other organism | GO:0044404 | 2.56E-02 |
oxygen and reactive oxygen species metabolism | GO:0006800 | 3.21E-02 |
complement activation | GO:0006956 | 3.21E-02 |
response to xenobiotic stimulus | GO:0009410 | 3.97E-02 |
lymphocyte differentiation | GO:0030098 | 3.94E-02 |
pathogenesis | GO:0009405 | 3.96E-02 |
T-helper 1 type immune response | GO:0042088 | 4.19E-02 |
detection of biotic stimulus | GO:0009595 | 4.49E-02 |
cytokine and chemokine mediated signaling pathway | GO:0019221 | 4.72E-02 |
antigen presentation, endogenous antigen | GO:0019883 | 4.71E-02 |
lymphocyte proliferation | GO:0046651 | 4.90E-02 |
antigen presentation | GO:0019882 | 8.19E-03 |
Angiogenesis
| ||
blood vessel morphogenesis | GO:0048514 | 8.92E-03 |
blood vessel development | GO:0001568 | 1.17E-02 |
angiogenesis | GO:0001525 | 1.47E-02 |
ECM
| ||
extracellular structure organization and biogenesis | GO:0043062 | 3.18E-02 |
extracellular matrix organization and biogenesis | GO:0030198 | 3.15E-02 |
cell-matrix adhesion | GO:0007160 | 4.31E-02 |
Signaling pathways
| ||
I-kappaB kinase/NF-kappaB cascade | GO:0007249 | 0.00E+00 |
regulation of I-kappaB kinase/NF-kappaB cascade | GO:0043122 | 2.38E-02 |
positive regulation of I-kappaB kinase/NF-kappaB cascade | GO:0043123 | 2.35E-02 |
Wnt receptor signaling pathway | GO:0016055 | 1.16E-04 |
Ras protein signal transduction | GO:0007265 | 4.61E-03 |
inactivation of MAPK | GO:0000188 | 2.43E-02 |
Steroid
| ||
steroid biosynthesis | GO:0006694 | 3.27E-06 |
sterol metabolism | GO:0016125 | 4.16E-02 |