IGFBP7 and Its Fuctions 浙江大学 来茂德等 IGFBP7 的 抗肿瘤效应 IGFBP7 的...
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IGFBP7 and Its FuctionsIGFBP7 and Its Fuctions
浙江大学浙江大学 来茂德来茂德等等
IGFBP7IGFBP7 的 抗肿瘤效应的 抗肿瘤效应
结直肠癌发生与发展结直肠癌发生与发展55qq
APCAPC1212pp
Ki-rasKi-ras
1818qqSmad4Smad4DCCDCC
Increase ofIncrease ofgenetic variationgenetic variation
Accumulation of Accumulation of 101044 - 10 - 101212 mutationsmutations
Chromosomal gains or lossesChromosomal gains or losses1010-2-2 per chromosome per generation per chromosome per generation
EarlyEarlyadenomaadenoma
LateLateadenomaadenoma
InvasiveInvasivecarcinomacarcinoma
MetastaticMetastaticcarcinomacarcinoma
NormalNormalepitheliumepithelium
1717ppp53p53
OtherOthermutationsmutations
55qqAPCAPC
1212ppKi-rasKi-ras
1818qqSmad4Smad4DCCDCC
MMRMMR DeficiencyDeficiency错配修复缺陷错配修复缺陷
VogelsteinVogelstein 模型模型 19901990
In 1999, by SSH, We constructed three librariesIn 1999, by SSH, We constructed three libraries
normalnormal adenoma cancerAPC, etc. P53,
etc.
TN A
The derivation of IGFBP7The derivation of IGFBP7
T N
B2
TTTT
TTTTB2
IGFBP7
97%
tester driver
World J Gastroenterol 2001;7(5):726-31
A B C D E MA B C D E M
5’-RACE5’-RACE
Gene card of IGFBP7Gene card of IGFBP7http://www.genecards.org/cgi-bin/carddisp.pl?gene=IGFBP7http://www.genecards.org/cgi-bin/carddisp.pl?gene=IGFBP7
Gene descriptionGene description: : insulin-like growth factor binding protein 7, belongs insulin-like growth factor binding protein 7, belongs
to the IGFBP familyto the IGFBP family Gene aliasesGene aliases: : FSTL2, IGFBP-rP1, MAC25, PSF, FSTL2, IGFBP-rP1, MAC25, PSF,
AGM,TAFAGM,TAF LocationLocation:4q12:4q12
282 AA
32 72 107 156160 264
IGFBP like Kazal likeKazal like Ig like
Signal peptide
I: IGFBP7 in colon cancer tissueI: IGFBP7 in colon cancer tissueIGFBP7IGFBP7 在癌组织中的表达在癌组织中的表达
F=6.29 , p=0.000; spearman’s rho=0.40,p=0.000
P25
N B A T0
0.5
1
1.5
2
IGFB
P7 A
U
N B A T
p75
p25
Expression of IGFBP7 at mRNA level in colorectal carcinomas (T), adenomas(A), tissue adjacent to tumor(B),and normal tissues(N)
从正常腺瘤到癌表达渐升高从正常腺瘤到癌表达渐升高
T vs. N, 2=12.05 ( df=1 ) , p<0.01
Immunohistochemistry result
11
65
32
46
30
85.5%
60%
60.5%
IHC of IGFBP7 in B and T in the same sample
Clin Cancer Res. 2007;13(17):5082-8
Overexpression of IGFBP7 correlated with favourable prognosis in CRC patients
Survival Functions
Éú´æʱ¼ä
14121086420-2
Cum
Surv
ival
1.1
1.0
.9
.8
.7
.6
.5
.4
BP7T×ÛºÏ
2.00
2.00-censored
1.00
1.00-censored
.00
.00-censored
IGFBP7IGFBP7 高表达预后好高表达预后好
LoVo HCT8 SW1116 RKO HT29 COLO205 Hce8693 CW2 SW620 SW480 Caco2 Control Marker
GAPDH
IGFBP7
IGFBP7 has a low expression in CRC IGFBP7 has a low expression in CRC cell linescell lines
II: The regulation mechanism of II: The regulation mechanism of
IGFBP7 in colon cancerIGFBP7 in colon cancer
Prediction of CpG islands of Prediction of CpG islands of IGFBP7IGFBP7
http://www.ebi.ac.uk/emboss/cpgblot/#andNewcpgseek; http://www.urogene.org/methprimer/index1.html
-355 +803
CpG island:
Length >200bp;
GC% >50%;
Obs./Exp. CpG >0.6
134
the putative promoter region, exon 1 and partial intron 1
Analyzing the methylation status of putative Analyzing the methylation status of putative promoter region, exon1, intron1 in 10 promoter region, exon1, intron1 in 10 cell linescell lines
using Bisulfite Sequencing PCR (BSP)using Bisulfite Sequencing PCR (BSP)
F1 R1F2 R2F3 R3F4
R4
Putative promoter Putative promoter regionregion
exon1exon1
intron1intron1
Methylation pattern of putative promoter Methylation pattern of putative promoter regionregion
HCT8
SW1116
HCE8693
COLO205
HT29
RKO
CW2
SW620
SW480
CACO2
HCT8
SW1116
HCE8693
COLO205
HT29
RKO
CW2
SW620
SW480
CACO2
-335 -329 -302 -298 -291 -286 -271 -251 -237 -223 -218 -214 -206 -202 -191 -185 -182 -174 -163 -160 -147 -146 -144 -142 -133 -131 -125 -117 -112 -108
-99 -88 -83 -69 -67 -58 -54 -49 -46 -35 -32 -28 -23 -18 -9 -7
methylationunmethylation
Intron 1Intron 1
HCT8
SW1116
HCE8693
COLO205
HT29
RKO
CW2
SW620
SW480
CACO2
+505 +509 +529 +532+536+544 +557+560+565 +569 +571+574+580 +585 +587 +599+608 +610+652+654+668 +675+678 +724 +728 +746+772 +801 +812
methylationunmethylation
Exon 1Exon 1
HCT8
SW1116
HCE8693
COLO205
HT29
RKO
CW2
SW620
SW480
CACO2
HCT8
SW1116
HCE8693
COLO205
HT29
RKO
CW2
SW620
SW480
CACO2
+3 +12 +19 +29 +33 +36 +41 +43 +55 +58 +6 +108 +118 +127 +132+144 +156 +175+182 +184+186+188 +193 +211 +215 +217 +220 +226 +233 +235
+244+247 +250+265 +267+270 +283 +293+302+316 +328+331 +336+346 +349+355+368 +375 +382+388 +391 +405+409+422 +424+427 +442+449 +451+490
methylationunmethylation
CW2 Hce8693 SW1116 HCT8 HT29 RKO COLO205 SW620 SW480 Caco2 Control Marker
M U M U M U M U M U M U M U M U M U M U
M, methylated product; U, unmethylated product; M-P, positive control of methylation; U-P, positive control of unmethylation; C, blank control of PCR system
unmethylation
Confirmation using MSPConfirmation using MSP
IGFBP7(+)
ClusterCluster analysis depending on the analysis depending on the methylation status of methylation status of exon 1exon 1
IGFBP7+
RestorationRestoration of IGFBP7 after 5-aza-dC treatment of IGFBP7 after 5-aza-dC treatment
RT-PCR
HT29
SW620COLO205
LoVo
Control Treated
ControlTreated
Immunohistochemistry
Methy-and deMethy sites of IGFBP-rP1Methy-and deMethy sites of IGFBP-rP1gene gene 5’-5’-regionregion
-- ,, controlcontrol ;; ++ ,, treated cellstreated cells ;; Black :methy-per centage Black :methy-per centage
J Pathol. 2007;212(1):83-90.J Pathol. 2007;212(1):83-90.
Methylation of IGFBP7 exon 1:the key regulationMethylation of IGFBP7 exon 1:the key regulationmechanism silencing IGFBP7 expression in CRC cellsmechanism silencing IGFBP7 expression in CRC cells外显子外显子 11 甲基化抑制基因表达甲基化抑制基因表达
Aberrant methylation Aberrant methylation
of IGFBP7 exon 1 in of IGFBP7 exon 1 in
colorectal cancer colorectal cancer
tissuestissues
在结直肠癌中的异常表达在结直肠癌中的异常表达
cases median P25 ~ P75 P
N 46 0.21 0.07 ~ 0.49 <0.001
T 46 0.61 0.30 ~ 0.85
Wilcoxon signed ranks test: Z=-5.131, Wilcoxon signed ranks test: Z=-5.131, PP<0.001<0.001N: matched colorectal normal tissue; T: colorectal cancer tissuesN: matched colorectal normal tissue; T: colorectal cancer tissues
RT-PCR of IGFBP7 in RT-PCR of IGFBP7 in colorectal cancer and matched colorectal cancer and matched normal tissuesnormal tissues
TT
NN
Expression of IGFBP7 protein in Expression of IGFBP7 protein in
colorectal cancer and matchedcolorectal cancer and matched
normal tissuesnormal tissues
0
5
10
15
20
25
30
35
40
N T
case
s
l ow
hi gh
0 1 2 3 P
N 11 26 8 1 0.007
T 6 23 13 4
Wilcoxon signed ranks test: Z=-2.674, Wilcoxon signed ranks test: Z=-2.674, PP=0.007=0.007N: matched colorectal normal tissue; T: colorectal cancer tissues; N: matched colorectal normal tissue; T: colorectal cancer tissues; 0, lack of staining; 1, mild staining; 2, intermediate staining; 3, strong staining0, lack of staining; 1, mild staining; 2, intermediate staining; 3, strong staining
ImmunohistochemiImmunohistochemical stainingcal staining
Expression of IGFBP7 protein in colorectal Expression of IGFBP7 protein in colorectal cancer and matched normal tissuescancer and matched normal tissues
MSP in colorectal MSP in colorectal cancer tissuescancer tissues
N, colorectal normal mucosa; T, colorectal cancer tissues; N, colorectal normal mucosa; T, colorectal cancer tissues;
M, methylated products; U, unmethylated products; M, methylated products; U, unmethylated products;
M-P, positive control of methylation; U-P, positive control of unmethylation; M-P, positive control of methylation; U-P, positive control of unmethylation;
C, blank control of PCR systemC, blank control of PCR system
0
5
10
15
20
25
30
35
40
N Tca
ses
unmethyl ati onmethyl ati on
Methylation status of Methylation status of
IGFBP7 in colorectal IGFBP7 in colorectal
cancer tissuecancer tissue
methylation unmethylation P
N 37 9 0.023
T 28 18
Wilcoxon signed ranks test: Z=-2.268, Wilcoxon signed ranks test: Z=-2.268, PP=0.023=0.023
N: matched colorectal normal mucosa;N: matched colorectal normal mucosa;T: colorectal cancer tissuesT: colorectal cancer tissues
mRNA Expression Methylation status (%)
P
N 0.21 80.4 0.044
T 0.61 60.9
Relationship between Relationship between
IGFBP7 expression and the IGFBP7 expression and the
exon 1 methylation statusexon 1 methylation status
r=-0.210, r=-0.210, PP=0.044=0.044
IHC unmethylation methylation P
Low (0, 1) 15 51 0.004
High (2, 3) 12 14
r=-0.299, r=-0.299, PP=0.004=0.004
III: The biological behaviour of IGFBP7 in III: The biological behaviour of IGFBP7 in
CRC cellsCRC cells 生物学行为生物学行为
IGFBP7 suppressed the growth of RKO IGFBP7 suppressed the growth of RKO cells and SW620 cellscells and SW620 cells 抑制癌细胞生长抑制癌细胞生长
RKORKO SW620SW620*, P=0.0066 IGFBP7-RKO transfectants versus control-vector transfectants,
**, P<0.0001 IGFBP7-SW620 transfectants versus SW620 control-vector transfectants.
***P=0.0108 SW480 versus SW620 cells
IGFBP7 reduced the soft agar colony IGFBP7 reduced the soft agar colony
formation ability of CRC cellsformation ability of CRC cells 减少集落形成减少集落形成
Control-RKO BP7-RKO Control-SW620 BP7-SW620
*, P=0.0004 for IGFBP7-RKO transfectants versus control
**, P=0.0026 for IGFBP7-SW620 transfectants versus control
Control-RKO BP7-RKO
Control-SW620 BP7-SW620
IGFBP7 suppressed the cell growth in soft agar
IGFBP7 induced apoptosis in CRC cellsIGFBP7 induced apoptosis in CRC cells诱导凋亡诱导凋亡
MTT
0
0. 5
1
1. 5
2
2. 5
0 1 2 3 4 5 6
处理时间(天)
(A)
吸光
值
对照2umol / L5umol / L10umol / L20umol / L
AA
BB
AZADCAZADC 抑制结肠癌细胞的生长(抑制结肠癌细胞的生长( AA )、促进凋亡()、促进凋亡( BB ))
Cancer Biol Ther. 2008;7(12):1896-900.Cancer Biol Ther. 2008;7(12):1896-900.
IGFBP-rP1IGFBP-rP1 inducing senescence inducing senescence 诱导老化诱导老化
Exp Mol Pathol. 2008;85(2):141-5.Exp Mol Pathol. 2008;85(2):141-5.
IGFBP7 was a potential tumor IGFBP7 was a potential tumor suppressor gene in colon cancersuppressor gene in colon cancer
是一个抑癌基因是一个抑癌基因
Cancer Biol Ther. 2007;6(3):354-9
Exp Mol Pathol. 2008;85(2):141-5
Explore the molecular Explore the molecular mechanism……mechanism……
IGFBP7 IGFBP7 transfectantstransfectants ControlControl
? ? What’s different insideWhat’s different inside
Identify the differentially expressed genes in IGFBP7-RKO transfectants versus control
RPRP55
RP6RP6 EVEV66
EVEV55
EVEV77
RP7RP7
vsvs vsvs
vsvs
EV5
RP5
RP7
RP6
EV6 EV7
cluster
Identify the differentially expressed genes using Affymetrix® Identify the differentially expressed genes using Affymetrix® GeneChip® U133 Plus 2.0GeneChip® U133 Plus 2.0
Reproducible in at least 2 clones: Reproducible in at least 2 clones: 9191 genes genes
KEGG pathway analysis: KEGG pathway analysis: MAPKMAPK pathway: pathway: GADD45BGADD45B ,, FOSFOS ,, FLNBFLNB ,, NR4A1NR4A1 , , RASA1 RASA1
TGF-TGF- pathway: pathway: SMAD3, CDKN2B, ID1, ID3SMAD3, CDKN2B, ID1, ID3
IGFBP7 could activate IGFBP7 could activate MAPKMAPK pathway and pathway and inhibit inhibit TGF-TGF- pathway.pathway.
Interesting information resides in the chip results:Interesting information resides in the chip results:
Reproductive in 3 clones: Reproductive in 3 clones: 1616 genes genesVerify the chip results(using realtime RT-PCR)Verify the chip results(using realtime RT-PCR)
Analysis of the 16 gene expression in IGFBP7-Analysis of the 16 gene expression in IGFBP7-SW620 transfectants and control. SW620 transfectants and control.
PH 5
Control-RKO ( EV) BP7-RKO (RP)
Comparative 2-DE of BP7-RKO and control8
EV RP EV RP
EV RP
EV RP
EV RPSpot Protein description Sequence
coverage(%)*
Swissprot ID
Theoretical Mr/Pi**
1 Serum albumin 5.74% P02768 69367/6.42
2 Serum albumin 7.97% P02768 69367/6.42
3 Serum albumin 6.86% P02768 69367/6.42
4 pyruvate kinase, muscle 22.45% Q9UK31 6002/7.58
5 Phenylalanyl-tRNA synthetase beta chain 12.56% Q9NSD9 66130/6.39
6 Actin, cytoplasmic 1or 2 33.33% P63261 41793/5.31
7 Actin, cytoplasmic 1or 2 23.20% P63261 41793/5.31
8 60 kDa heat shock protein, mitochondrial precursor
2.96% P10809 61055/5.7
9 60 kDa heat shock protein, mitochondrial precursor
28.52% P10809 61055/5.7
*Sequence coverage was calculated by amino acid count
**Calculated from the database entry without any processing
Unpublished data
The association between IGFBP7 and fasting glucose
IGFBP7 表达与空腹血糖相关
B2
3. 002. 001. 00. 00
Mean
GLU
COSE
6. 4
6. 2
6. 0
5. 8
5. 6
5. 4
5. 2
5. 0
Expression level of IGFBP7
•Endocr Relat Cancer. 2004;11(1):141-8.
y = 0. 1158Ln(x) + 0. 5555R2 = 0. 9789
0
0. 2
0. 4
0. 6
0. 8
1
1. 2
1. 4
0 100 200 300 400 500
(ng/ ml )抗原浓度
OD
(450
nm)
Standard curve
(ng/mL)
Evaluate IGFBP7 level in serum in patients of type 2 diabetes using Elisa
Healthy personsHealthy persons
Frequency of donor’s ageFrequency of donor’s age
ageage
CRC and DM CRC and DM VSVS healthy persons healthy persons
结直肠癌正常人群
50.000
40.000
30.000
20.000
10.000
0.000
IGFB
P-r
P1(u
g/L
)
IGF
BP
-rP
1(µ
g/L
)IG
FB
P-r
P1(
µg/
L)
Healthy persons CRC patientsHealthy persons CRC patients
3T3-L1 preadipoctytes
(×100)
3T3-L1 adipocytes (stain with Oil Red-O) (×100)
3T3-L1 adipocytes
(×100)
IGFBP7 inhibit insulin-stimulated 2-deoxyglucose (DOG) Uptake in 3T3-L1 adipocytes
Metabolic syndrome is Metabolic syndrome is reversiblereversible
代谢综合征是二十一世纪流行病,可逆代谢综合征是二十一世纪流行病,可逆
112233
44 556677
ALSALS
IGF-IIGF-I insulininsulin
extracellularextracellular
??intracellularintracellular
IGFBP-RIGFBP-R
IGFBP-rpRIGFBP-rpRIGF-IRIGF-IR Insulin RInsulin R
MAPKMAPK PI3kPI3k
Mechanism of IGFBP-rP1Mechanism of IGFBP-rP1Burger et al. Eur J Cancer, 41: 1515-1527, 2005Burger et al. Eur J Cancer, 41: 1515-1527, 2005
IGFBP7 may be a molecule contribute to insulin resistance, which may play important roles in the initiation and development of type 2 diabetes.
可能参与 2 型糖尿病的发生和发展
•Unpublished data
IGFBP7 binds insulin with high affinity:IGFBP7 binds insulin with high affinity: 500 fold higher than IGFBP1-6 does.500 fold higher than IGFBP1-6 does.
What’s the binding structure of IGFBP7 to insulin?What’s the binding structure of IGFBP7 to insulin?
Character of IGFBP7Character of IGFBP7
J Biol Chem. 1997;272(49):30729-34.
amino sequence: 172-176amino sequence: 172-176 ,, 196-201196-201 ,, 217-220217-220 ,, 235-244235-244
Predicting the binding domain of IGFBP7 to Predicting the binding domain of IGFBP7 to insulin:insulin:
ATGGAGCGGCCGTCGCTGCGCGCCCTGCTCCTCGGCGCCGCTGGGCTGCTGCTCCTGCTCCTGCCCCTCTCATGGAGCGGCCGTCGCTGCGCGCCCTGCTCCTCGGCGCCGCTGGGCTGCTGCTCCTGCTCCTGCCCCTCTCCTCTTCCTCCTCTTCGGACACCTGCGGCCCCTGCGAGCCGGCCTCCTGCCCGCCCCTGCCCCCGCTGGCTCTTCCTCCTCTTCGGACACCTGCGGCCCCTGCGAGCCGGCCTCCTGCCCGCCCCTGCCCCCGCTGGGCTGCCTGCTGGGCGAGACCCGCGACGCGTGCGGCTGCTGCCCTATGTGCGCCCGCGGCGAGGGCGGCTGCCTGCTGGGCGAGACCCGCGACGCGTGCGGCTGCTGCCCTATGTGCGCCCGCGGCGAGGGCGAGCCGTGCGGGGGTGGCGGCGCCGGCAGGGGGTACTGCGCGCCGGGCATGGAGTGCGTGAAGAGCAGCCGTGCGGGGGTGGCGGCGCCGGCAGGGGGTACTGCGCGCCGGGCATGGAGTGCGTGAAGAGCCGCAAGAGGCGGAAGGGTAAAGCCGGGGCAGCAGCCGGCGGTCCGGGTGTAAGCGGCGTGTGCGTCGCAAGAGGCGGAAGGGTAAAGCCGGGGCAGCAGCCGGCGGTCCGGGTGTAAGCGGCGTGTGCGTGTGCAAGAGCCGCTACCCGGTGTGCGGCAGCGACGGCACCACCTACCCGAGCGGCTGCCAGCTGCGGTGCAAGAGCCGCTACCCGGTGTGCGGCAGCGACGGCACCACCTACCCGAGCGGCTGCCAGCTGCGCGCCGCCAGCCAGAGGGCCGAGAGCCGCGGGGAGAAGGCCATCACCCAGGTCAGCAAGGGCACCTCGCCGCCAGCCAGAGGGCCGAGAGCCGCGGGGAGAAGGCCATCACCCAGGTCAGCAAGGGCACCTGCGAGCAAGGTCCTTCCATAGTGACGCCCCCCAAGGACATCTGGAATGCGAGCAAGGTCCTTCCATAGTGACGCCCCCCAAGGACATCTGGAATGTCACTGGTGCCCAGGTCACTGGTGCCCAGGTGTAGTGTACTTGAGCTGTGAGGTCATCGGAATCCCGACACCTGTCCTCATCTGGAACAAGCTTGAGCTGTGAGGTCATCGGAATCCCGACACCTGTCCTCATCTGGAACAAGGTAAAAAGGGGTCAGTAAAAAGGGGTCACTATCTATGGAGTTCAAAGGACAGAACTCCTGCCTGGTGACCGGGACAACCTGGGAGTTCAAAGGACAGAACTCCTGCCTGGTGACCGGGACAACCTGGCCATTCAGACCGCCATTCAGACCCGGGGCGGGGTGGCCCAGAAAAGCATGAAGTAACTGGCTGGGTGCTGTGGCCCAGAAAAGCATGAAGTAACTGGCTGGGTGCTGGTATCTCCTCTAAGTAAGGAAGATGCTGGGTATCTCCTCTAAGTAAGGAAGATGCTGGAAGAATATGAGTGCCATGCATCCAATTCCCAAGGACAGGCTTCAGCATCAGCAAAAATTACAGTGGTGAATATGAGTGCCATGCATCCAATTCCCAAGGACAGGCTTCAGCATCAGCAAAAATTACAGTGGTTGATGCCTTACATGAAATACCAGTGAAAAAAGGTGAAGGTGCCGAGCTATAATGATGCCTTACATGAAATACCAGTGAAAAAAGGTGAAGGTGCCGAGCTATAA
CN P
W
Prote
in M
arke
r
Who
le BL2
1 lys
ate
With
out W
Super
nata
nt o
f
sonic
ated
BL2
1
Precip
itate
of
sonic
ated
BL2
1
Purifie
d fu
sion
prot
ein
W-p
ET28a
Prote
in M
arke
r
Who
le BL2
1 lys
ate
With
out I
Super
nata
nt o
f
sonic
ated
BL2
1
Precip
itate
of
sonic
ated
BL2
1
Purifie
d fu
sion
prot
ein
I-pET41
a
Prote
in M
arke
r
Who
le BL2
1 lys
ate
With
out 0
1
Super
nata
nt o
f
sonic
ated
BL2
1
Precip
itate
of
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BL2
1
Purifie
d fu
sion
prot
ein
01-p
ET28a
Prote
in M
arke
r
Who
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1 lys
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With
out 0
2
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nata
nt o
f
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BL2
1
Precip
itate
of
sonic
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BL2
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Purifie
d fu
sion
prot
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02-p
ET41a
W-pET28a(+) P-pET41a(+)
N-pET28a(+) C-pET41a(+)
Express the fragments of IGFBP7Express the fragments of IGFBP7
W P N C
Insulin
SDS-PAGEcut the gel at 6KD
transmembrane
Incubated with
fusion proteinwith His-tag
wash
Incubated with His-tag Ab
wash
Incubated with secondary Ab
For odssey
Analyze the binding affinity of the IGFBP7 fragments to insulinAnalyze the binding affinity of the IGFBP7 fragments to insulin
正在对关键氨基酸进行鉴定正在对关键氨基酸进行鉴定
Conclusions Conclusions 1.The expression of IGFBP7 was upregulated in CRC The expression of IGFBP7 was upregulated in CRC
tissue. Overexpression of IGFBP7 correlates with tissue. Overexpression of IGFBP7 correlates with
favourable prognosis in CRC patients.favourable prognosis in CRC patients.
2.Methylation of exon1 was the key regulating mechanism Methylation of exon1 was the key regulating mechanism
of IGFBP7.of IGFBP7.
3. IGFBP7 played potential tumor suppressor role in IGFBP7 played potential tumor suppressor role in
colorectal carcinogenesis.colorectal carcinogenesis.
4.The patients with insulin resistance are associated with higher incidence of some cancers.The serum IGFBP7 The serum IGFBP7 level was higher in type 2 diabetes and colorectal cancer level was higher in type 2 diabetes and colorectal cancer patients. IGFBP7 may be a molecule contributing to patients. IGFBP7 may be a molecule contributing to insulin resistance.insulin resistance.
GrantsGrants China National “973” program China National “973” program (( 2007CB914302007CB91430
44 ))
the National Scientific Foundation of China the National Scientific Foundation of China
(30200333, 30570840, 30770989, 30900236)(30200333, 30570840, 30770989, 30900236)
Zhejiang Natural Science Foundation of China Zhejiang Natural Science Foundation of China (( D2080011D2080011 ))
Persons contributed to the researchDepartment of PathologyDepartment of Pathology, ,
Zhejiang UniversityZhejiang University
Dr. Maode LaiDr. Maode Lai
Dr. Minjie LuoDr. Minjie Luo
Dr. Lina ShaoDr. Lina Shao
Dr. Jie LinDr. Jie Lin
Dr. Wenjing RuanDr. Wenjing Ruan
Dr. Yu MaDr. Yu Ma
Dr. Fangying XuDr. Fangying Xu
Lipei WangLipei Wang
Haibing WangHaibing Wang
Youzhao LiYouzhao Li
……
Department of ChemistryDepartment of Chemistry, ,
Zhejiang UniversityZhejiang University
Dr. Tao WuDr. Tao WuDr. Xin Dr. Xin ChenChen