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Cornelia Siebenkäs, Katherine B. Chiappinelli, Angela A. Guzzetta, Anup Sharma, Jana Jeschke, Rajita Vatapalli, Stephen B. Baylin, Nita Ahuja
Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells
www.plosone.org
www.plosone.org
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(CAOV3,)Tj
3.6454 0 Td
(DOV13,)Tj
3.5149 0 Td
(EFO27,)Tj
3.1805 0 Td
(ES2,)Tj
-35.2571 -1.2983 Td
(Hey,)Tj
2.0522 0 Td
(HEYC2,)Tj
3.4923 0 Td
(Kuramochi,)Tj
4.8982 0 Td
(OAW28,)Tj
3.7304 0 Td
(OAW42,)Tj
3.736 0 Td
(OV167,)Tj
3.2542 0 Td
(OV2008,)Tj
3.719 0 Td
(OV90,)Tj
2.7836 0 Td
(OVCA429,)Tj
4.5808 0 Td
(OVCA432,)Tj
-32.2467 -1.2982 Td
(OVMANA,)Tj
4.8131 0 Td
(OVCAR3,)Tj
4.2633 0 Td
(OVCAR5,)Tj
4.2576 0 Td
(OVKATE,)Tj
4.354 0 Td
(PEO14,)Tj
3.2145 0 Td
(SKOV3,)Tj
3.4526 0 Td
(TOV112D,)Tj
4.5807 0 Td
(and)Tj
1.7008 0 Td
(TykNu;)Tj
3.2088 0 Td
(these)Tj
-33.8454 -1.3039 Td
(were)Tj
2.0806 0 Td
(maintained)Tj
4.6884 0 Td
(under)Tj
2.5682 0 Td
(the)Tj
1.44 0 Td
(ATCC)Tj
2.8063 0 Td
(recommended)Tj
5.9244 0 Td
(conditions.)Tj
4.5921 0 Td
(Cells)Tj
2.1089 0 Td
(were)Tj
2.0806 0 Td
(treated)Tj
2.931 0 Td
(with)Tj
1.9559 0 Td
(500)Tj
1.6158 0 Td
(nM)Tj
1.6441 0 Td
(of)Tj
-36.4363 -1.2983 Td
(5-AC)Tj
2.3527 0 Td
(\(Sigma\))Tj
3.2938 0 Td
(every)Tj
2.2961 0 Td
(24)Tj
1.1508 0 Td
(hours)Tj
2.4662 0 Td
(for)Tj
1.3549 0 Td
(3)Tj
0.686 0 Td
(consecutive)Tj
4.7678 0 Td
(days)Tj
1.9559 0 Td
(and)Tj
1.7008 0 Td
(harvested)Tj
3.9515 0 Td
(at)Tj
0.9354 0 Td
(3,)Tj
0.9014 0 Td
(7,)Tj
0.9014 0 Td
(10,)Tj
1.3663 0 Td
(14,)Tj
1.3663 0 Td
(and)Tj
1.7008 0 Td
(21)Tj
1.1508 0 Td
(days)Tj
-34.2989 -1.2983 Td
(after)Tj
1.9842 0 Td
(the)Tj
1.44 0 Td
(beginning)Tj
4.1726 0 Td
(of)Tj
0.9921 0 Td
(treatment.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 497.1401 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(RNA)Tj
2.3102 0 Td
(extraction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 480.1322 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Cells)Tj
2.1599 0 Td
(were)Tj
2.1203 0 Td
(harvested)Tj
4.0422 0 Td
(with)Tj
1.9956 0 Td
(TRIzol)Tj
2.9593 0 Td
(\(Invitrogen\))Tj
5.1251 0 Td
(according)Tj
4.1895 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(manufacturer's)Tj
6.2645 0 Td
(protocol)Tj
3.5943 0 Td
(with)Tj
-34.9452 -1.2982 Td
(the)Tj
1.4683 0 Td
(exception)Tj
4.0932 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(additional)Tj
4.2803 0 Td
(ethanol)Tj
3.2031 0 Td
(washing)Tj
3.5093 0 Td
(step)Tj
1.8198 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.652 0 Td
(subsequent)Tj
4.7055 0 Td
(clean-up)Tj
3.6963 0 Td
(via)Tj
1.372 0 Td
(the)Tj
1.4683 0 Td
(RNeasy)Tj
-34.2139 -1.3039 Td
(Mini)Tj
2.194 0 Td
(kit)Tj
1.2812 0 Td
(\(Qiagen\).)Tj
4.0138 0 Td
(Normal)Tj
3.3336 0 Td
(colon)Tj
2.4491 0 Td
(total)Tj
2.0069 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.6951 0 Td
(obtained)Tj
3.7361 0 Td
(from)Tj
2.2053 0 Td
(BioChain)Tj
4.0138 0 Td
(as)Tj
1.0148 0 Td
(RNA)Tj
2.2621 0 Td
(isolated)Tj
-32.4678 -1.2983 Td
(from)Tj
2.2053 0 Td
(a)Tj
0.652 0 Td
(pool)Tj
2.0012 0 Td
(of)Tj
1.0148 0 Td
(5)Tj
0.6916 0 Td
(human)Tj
3.0785 0 Td
(colon)Tj
2.4547 0 Td
(donors)Tj
3.0388 0 Td
(\(#R1234090-P\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 411.9874 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Quantitative)Tj
5.4992 0 Td
(RT-PCR)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 394.9795 cm
BT
/F6 1 Tf
1 TL
-0.004 Tc
0 0 Td
(For)Tj
1.627 0 Td
(colon)Tj
2.4491 0 Td
(cancer)Tj
2.846 0 Td
(cell)Tj
1.5591 0 Td
(lines,)Tj
2.2903 0 Td
(1)Tj
/F12 1 Tf
[()]TJ
/F6 1 Tf
(g)Tj
1.6668 0 Td
(of)Tj
1.0148 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.7008 0 Td
(transcribed)Tj
4.7508 0 Td
(into)Tj
1.8425 0 Td
(cDNA)Tj
2.8007 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4683 0 Td
(SuperScriptTM)Tj
-30.6706 -1.2982 Td
(III)Tj
1.2415 0 Td
(First-Strand)Tj
5.0513 0 Td
(Synthesis)Tj
3.9345 0 Td
(System)Tj
3.0557 0 Td
(for)Tj
1.3833 0 Td
(RT-PCR)Tj
3.6453 0 Td
(\(Invitrogen\))Tj
5.1251 0 Td
(according)Tj
4.1895 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(manufacturer's)Tj
-30.1207 -1.2983 Td
(instructions.)Tj
5.2213 0 Td
(cDNA)Tj
2.8006 0 Td
(was)Tj
1.7008 0 Td
(diluted)Tj
3.0387 0 Td
(1:10)Tj
1.8709 0 Td
(and)Tj
1.7291 0 Td
(used)Tj
2.0636 0 Td
(for)Tj
1.3833 0 Td
(subsequent)Tj
4.7055 0 Td
(qRT-PCR)Tj
4.1556 0 Td
(with)Tj
1.9956 0 Td
(1x)Tj
1.1622 0 Td
(Power)Tj
2.7665 0 Td
(SYBR)Tj
-34.5937 -1.3039 Td
(Green)Tj
2.6985 0 Td
(PCR)Tj
2.0693 0 Td
(Master)Tj
2.999 0 Td
(Mix)Tj
1.8425 0 Td
(\(Applied)Tj
3.7474 0 Td
(Biosystems\).)Tj
5.2157 0 Td
(0.2)Tj
1.3947 0 Td
(pmol)Tj
2.313 0 Td
(of)Tj
1.0148 0 Td
(each)Tj
2.0296 0 Td
(primer)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(5)Tj
/F12 1 Tf
0.6974 0 Td
[()]TJ
/F6 1 Tf
(l)Tj
0.9751 0 Td
(cDNA)Tj
2.8006 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
-35.5462 -1.2983 Td
(total)Tj
2.0012 0 Td
(volume)Tj
3.1975 0 Td
(of)Tj
1.0148 0 Td
(25)Tj
/F12 1 Tf
1.1735 0 Td
[()]TJ
/F6 1 Tf
(l.)Tj
1.1962 0 Td
(All)Tj
1.4003 0 Td
(samples)Tj
3.3789 0 Td
(were)Tj
2.126 0 Td
(measured)Tj
4.1102 0 Td
(in)Tj
1.0318 0 Td
(triplicate)Tj
3.77 0 Td
(with)Tj
1.9956 0 Td
(35)Tj
1.1735 0 Td
(cycles)Tj
2.5512 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4684 0 Td
(optimal)Tj
-32.5415 -1.2982 Td
(annealing)Tj
4.1328 0 Td
(temperature)Tj
5.1307 0 Td
(of)Tj
1.0148 0 Td
(each)Tj
2.0296 0 Td
(primer)Tj
2.9877 0 Td
(in)Tj
1.0375 0 Td
(an)Tj
1.2019 0 Td
(AB)Tj
1.4853 0 Td
(StepOnePlus)Tj
5.3461 0 Td
(Real-Time)Tj
4.4164 0 Td
(PCR)Tj
2.0636 0 Td
(System)Tj
3.0557 0 Td
(\(Applied)Tj
-33.9021 -1.2983 Td
(Biosystems\).)Tj
5.2157 0 Td
(Resulting)Tj
3.9798 0 Td
(data)Tj
1.9162 0 Td
(was)Tj
1.6951 0 Td
(analyzed)Tj
3.702 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
/F13 1 Tf
1.4684 0 Td
( )Tj
/F6 1 Tf
(Ct)Tj
2.3641 0 Td
(method.)Tj
3.5489 0 Td
(Melting)Tj
3.3619 0 Td
(curve)Tj
2.4208 0 Td
(analyses)Tj
3.4809 0 Td
(were)Tj
-35.5462 -1.3039 Td
(performed)Tj
4.4673 0 Td
(in)Tj
1.0375 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(visualize)Tj
3.6113 0 Td
(potential)Tj
3.7587 0 Td
(by-products.)Tj
5.2951 0 Td
(Only)Tj
2.2167 0 Td
(results)Tj
2.8063 0 Td
(with)Tj
2.0012 0 Td
(one)Tj
1.6951 0 Td
(melting)Tj
3.2882 0 Td
(curve)Tj
-33.6243 -1.2983 Td
(peak)Tj
2.0919 0 Td
(were)Tj
2.1203 0 Td
(used)Tj
2.0579 0 Td
(for)Tj
1.389 0 Td
(subsequent)Tj
4.7055 0 Td
(analysis.)Tj
-11.1684 -1.2982 Td
(For)Tj
1.627 0 Td
(primary)Tj
3.4583 0 Td
(tissue)Tj
2.4548 0 Td
(specimens,)Tj
4.5921 0 Td
(we)Tj
1.3266 0 Td
(used)Tj
2.0636 0 Td
(a)Tj
0.6519 0 Td
(total)Tj
2.0013 0 Td
(of)Tj
1.0148 0 Td
(7)Tj
0.6973 0 Td
(samples)Tj
3.3846 0 Td
(\(4)Tj
1.0318 0 Td
(primary)Tj
3.4582 0 Td
(colon)Tj
2.4548 0 Td
(adenocarci-)Tj
-31.4133 -1.304 Td
(noma)Tj
2.5284 0 Td
(tumor)Tj
2.744 0 Td
(samples)Tj
3.3845 0 Td
(and)Tj
1.7291 0 Td
(3)Tj
0.6917 0 Td
(normal)Tj
3.1521 0 Td
(colon)Tj
2.4491 0 Td
(tissues\))Tj
3.1578 0 Td
(obtained)Tj
3.736 0 Td
(from)Tj
2.2054 0 Td
(the)Tj
1.4683 0 Td
(study)Tj
2.3924 0 Td
(approved)Tj
3.9685 0 Td
(by)Tj
1.1849 0 Td
(Insti-)Tj
-34.7922 -1.2982 Td
(tutional)Tj
3.3448 0 Td
(Review)Tj
3.0954 0 Td
(Board)Tj
2.6419 0 Td
(\(IRB\).)Tj
2.6645 0 Td
(The)Tj
1.7859 0 Td
(tumor)Tj
2.7439 0 Td
(specimens)Tj
4.3596 0 Td
(were)Tj
2.126 0 Td
(macro-dissected)Tj
6.7408 0 Td
(to)Tj
1.0204 0 Td
(avoid)Tj
2.4151 0 Td
(any)Tj
-32.9383 -1.2983 Td
(surrounding)Tj
5.244 0 Td
(stromal)Tj
3.2542 0 Td
(tissue.)Tj
2.6872 0 Td
(All)Tj
1.3946 0 Td
(samples)Tj
3.3846 0 Td
(underwent)Tj
4.5694 0 Td
(RNA)Tj
2.262 0 Td
(extraction)Tj
4.2576 0 Td
(followed)Tj
3.651 0 Td
(by)Tj
1.1792 0 Td
(gene)Tj
2.0807 0 Td
(expres-)Tj
-33.9645 -1.3039 Td
(sion)Tj
1.9048 0 Td
(analysis)Tj
3.3222 0 Td
(as)Tj
1.0148 0 Td
(shown)Tj
2.8516 0 Td
(above.)Tj
2.7723 0 Td
(A)Tj
0.9014 0 Td
(qPCR)Tj
2.5682 0 Td
(expression)Tj
4.4674 0 Td
(level)Tj
2.0125 0 Td
(of)Tj
1.0148 0 Td
(7)Tj
0.6974 0 Td
(candidate)Tj
4.1045 0 Td
(genes)Tj
2.4435 0 Td
(B2M,)Tj
2.3924 0 Td
(CD58,)Tj
-32.4678 -1.2983 Td
(PSMB8,)Tj
3.4242 0 Td
(PSMB9,)Tj
3.4299 0 Td
(TAPBP,)Tj
3.4412 0 Td
(CALR)Tj
2.7269 0 Td
(and)Tj
1.7292 0 Td
(TAP1)Tj
2.5511 0 Td
(was)Tj
1.6951 0 Td
(measured)Tj
4.1102 0 Td
(in)Tj
1.0375 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4683 0 Td
(fresh)Tj
2.194 0 Td
(frozen)Tj
2.7723 0 Td
(samples.)Tj
3.6057 0 Td
(We)Tj
-35.3308 -1.2982 Td
(used)Tj
2.0579 0 Td
(glyceraldehyde)Tj
6.1681 0 Td
(3-phosphate)Tj
5.1647 0 Td
(dehydrogenase)Tj
6.2135 0 Td
(\(GAPDH\))Tj
4.3597 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(housekeeping)Tj
5.709 0 Td
(gene)Tj
2.0806 0 Td
(to)Tj
1.0261 0 Td
(nor-)Tj
-34.452 -1.3039 Td
(malize)Tj
2.8232 0 Td
(gene)Tj
2.0807 0 Td
(expression.)Tj
-3.7077 -1.2983 Td
(F)Tj
-0.014 Tc
(or)Tj
1.61 0 Td
(ovarian)Tj
3.1635 0 Td
(cancer)Tj
2.7836 0 Td
(cell)Tj
1.525 0 Td
(lines,)Tj
2.228 0 Td
(after)Tj
1.9843 0 Td
(total)Tj
1.9559 0 Td
(cellular)Tj
3.0614 0 Td
(RNA)Tj
2.228 0 Td
(was)Tj
1.6724 0 Td
(extracted)Tj
3.7927 0 Td
(using)Tj
2.3414 0 Td
(the)Tj
1.44 0 Td
(Trizol)Tj
2.5739 0 Td
(method)Tj
-33.5563 -1.2983 Td
(\(Life)Tj
2.0239 0 Td
(Technologies,)Tj
5.6295 0 Td
(Carlsbad,)Tj
3.9005 0 Td
(California\),)Tj
4.6885 0 Td
(RNA)Tj
2.2337 0 Td
(concentration)Tj
5.6919 0 Td
(was)Tj
1.6667 0 Td
(determined)Tj
4.7509 0 Td
(using)Tj
2.3414 0 Td
(the)Tj
1.44 0 Td
(Nano-)Tj
-34.367 -1.2982 Td
(drop)Tj
2.1032 0 Td
(machine)Tj
3.5944 0 Td
(and)Tj
1.7007 0 Td
(software)Tj
3.5036 0 Td
(\(Thermo)Tj
3.7531 0 Td
(Fisher)Tj
2.6362 0 Td
(Scientific,)Tj
4.0195 0 Td
(Rockville,)Tj
4.0308 0 Td
(Maryland\).)Tj
4.5978 0 Td
(1)Tj
/F12 1 Tf
0.686 0 Td
[()]TJ
/F6 1 Tf
(g)Tj
1.1678 0 Td
(total)Tj
1.9559 0 Td
(RNA)Tj
2.2337 0 Td
(was)Tj
-35.9827 -1.304 Td
(used)Tj
2.0182 0 Td
(to)Tj
1.0035 0 Td
(generate)Tj
3.5319 0 Td
(cDNA)Tj
2.7609 0 Td
(with)Tj
1.9559 0 Td
(the)Tj
1.44 0 Td
(QuantiTect)Tj
4.6998 0 Td
(Reverse)Tj
3.2258 0 Td
(Transcription)Tj
5.6183 0 Td
(Kit)Tj
1.4286 0 Td
(\(Qiagen,)Tj
3.5887 0 Td
(Venlo,)Tj
2.8062 0 Td
(The)Tj
-34.0778 -1.2982 Td
(Netherlands\).)Tj
5.5502 0 Td
(Quantitative)Tj
5.1023 0 Td
(reverse)Tj
2.9763 0 Td
(transcription)Tj
5.3065 0 Td
(PCR)Tj
2.0352 0 Td
(\(q-RT-PCR\))Tj
5.0797 0 Td
(of)Tj
/F11 1 Tf
0.9978 0 Td
[()9()]TJ
/F6 1 Tf
2.6362 0 Td
(mRNA)Tj
3.0387 0 Td
(was)Tj
1.6724 0 Td
(per-)Tj
-34.3953 -1.2983 Td
(formed)Tj
3.0954 0 Td
(using)Tj
2.3414 0 Td
(a)Tj
0.6406 0 Td
(TaqMan)Tj
3.5886 0 Td
(assay)Tj
2.2167 0 Td
(and)Tj
1.7008 0 Td
(the)Tj
1.44 0 Td
(Applied)Tj
3.3335 0 Td
(Biosystems)Tj
4.5524 0 Td
(7500)Tj
2.0806 0 Td
(Fast)Tj
1.8029 0 Td
(real-time)Tj
3.7643 0 Td
(PCR)Tj
2.0353 0 Td
(system)Tj
2.8743 0 Td
(and)Tj
-35.4668 -1.3039 Td
(software.)Tj
3.719 0 Td
(TATA)Tj
2.7722 0 Td
(Binding)Tj
3.3562 0 Td
(Protein)Tj
3.1238 0 Td
(\(TBP\))Tj
2.6022 0 Td
(was)Tj
1.6668 0 Td
(used)Tj
2.0182 0 Td
(as)Tj
0.9978 0 Td
(a)Tj
0.6406 0 Td
(reference)Tj
3.8324 0 Td
(gene.)Tj
2.2564 0 Td
(The)Tj
/F13 1 Tf
1.7518 0 Td
( )Tj
/F6 1 Tf
(CT)Tj
2.6305 0 Td
(method)Tj
3.2655 0 Td
(was)Tj
-34.6334 -1.2983 Td
(used)Tj
2.0182 0 Td
(to)Tj
1.0035 0 Td
(calculate)Tj
3.5886 0 Td
(relative)Tj
3.0614 0 Td
(expression)Tj
4.3653 0 Td
(levels.)Tj
2.5285 0 Td
(All)Tj
1.3663 0 Td
(qRT-PCR)Tj
4.0875 0 Td
(assays)Tj
2.5625 0 Td
(were)Tj
2.0807 0 Td
(carried)Tj
2.9706 0 Td
(out)Tj
1.5251 0 Td
(in)Tj
1.0148 0 Td
(triplicate)Tj
3.668 0 Td
(and)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 282.1039 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Inhibiting)Tj
4.1386 0 Td
(DNA)Tj
2.3031 0 Td
(methylation)Tj
5.2442 0 Td
(activates)Tj
4.0961 0 Td
(antigens)Tj
3.9331 0 Td
(and)Tj
1.8496 0 Td
(antigen)Tj
3.437 0 Td
(presentation)Tj
5.6268 0 Td
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