EGR1 regulate radiation-induced apoptosis in human head and neck squamous cell cancer Tae Mi Yoon 1 *, Sun Yea Kim 1 , Joon Kyoo Lee 1 , Young Lan Park 2 , Young Eun Joo 2 , Jae Hyuk Lee 3 and Sang Chul Lim 1 Department of 1 Otorhinolaryngology–Head and Neck Surgery, 2 Internal Medicine, 3 Pathology, Chonnam National University Medical school, Hwasun Hospital Introduction Results Conclusion EGR-1 had abundant expression in human HNSCC tissue. EGR-1 knockdown inhibited radiation-induced apoptosis through caspase 3, caspase, 7, PARP. EGR-1 may play an important role in treatment response after radiation therapy in human HNSCC. Figure 4. Radiation upragulates EGR1 expression in human HNSCC. After 5Gy and 8Gy irradiation, mRNA and protein expression of Egr1 increased with peak activation from 30 min to 2 h. Figure 5. The activation of apoptosis related proteins after radiation in human HNSCC cells. The cleaved caspase 3, cleaved caspase 7, and cleaved PARP were increased at 2 h after irradiation in SNU1041 and PCI50. pro-apoptotic protein Bax was also increased at 2 h after irradiation in PCI50. . To investigate that the early growth response-1 (EGR1) expression in human head and neck squamous cancer (HNSCC) and to evaluate whether EGR1 affects radiation-induced apoptosis and it would thus serves as the proper prognostic biomolecular marker of radiation therapy in human HNSCC . Aims Summary EGR1 have abundant expression in human hypopharyngeal cancer tissue Radiation up-regulate EGR1 proteins in human HNSCC cell lines. Radiation up-regulate apoptosis related proteins in human HNSCC cell lines. Knockdown of EGR1 inhibits radiation induced apoptosis in human HNSCC cell line. Knockdown of EGR1 inhibits the activation of apoptosis related proteins in human HNSCC cell line. Figure 6. The change of apoptosis related proteins by EGR1 knock down after radiation in human HNSCC cells. The cleaved caspase 3, cleaved caspase 7, cleaved PARP activation was decreased, and XIAP activation was increased by EGR-1 knock down after irradiation Figure 7. Effect of EGR1 on cell apoptosis after radiation in human HNSCC cells. EGR-1 knockdown (E) inhibited radiation-induced apoptosis, compared with control cells (C) in cell apoptosis assay. Table 1. Clinicopathologic variables of 28 patients with advanced hypopharyngeal cancer Figure 1. Expression of EGR1 (A) Immunohistochemical stainig of Livin in human hypopharyngeal cancer tissues. Egr-1 immunoreactivity showed intense nuclear staining relative to adjacent tissue mucosa. (B) mRNA expression of EGR1 increased in tumor tissue compared with normal mucosa. Figure 2. The survival curve according to EGR1 expression in human hypopharyngeal cancer - Mean duration of overall survival in the negative EGR1 group vs positive EGR1 group : 41.4 months vs 53.6 months The expression and function of EGR1 EGR1 over-expressed the variable cancer cells (esophagus, prostate, bladder, breast, stomach, colon) EGR1 is oncogene or tumor suppresser gene ? - cancer progression, cell growth vs apoptosis ? -ongogenic function in prostate cancer - Positive prognostic effect on survival in nasopharyngeal cancer Variables Value Age (y): mean±SD (range) 63.18±7.91 (51-83) Sex (male:female) 27:1 Location (piriform sinus:post. pharyngeal wall) 22:6 Stage (III : IV) 8:20 T stage (T1:T2:T3:T4) 1:14:6:7 N stage (N0:N1:N2) 2:10:16 Distant metastasis (M0:M1) 24:4 Tumor response after NC (CR,PR:NR) 27:1 Overall tumor response after CRT (CR:PR,NR) 22:6 Recurrence (no recur: recur) 10:12 3 year Overall survival (%) 46 A B *100 *200 Figure 3. EGR1 expression and knock down by siRNA in human head and neck squamous carcinoma cell lines SNU 1041 PCI50 SNU 1041 PCI50 PCI50 No treatment 24hr after 5 cGy radiation
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EGR1 regulate radiation-induced apoptosis in human head and neck squamous cell cancer
Tae Mi Yoon1*, Sun Yea Kim1, Joon Kyoo Lee1, Young Lan Park2, Young Eun Joo2, Jae Hyuk Lee3 and Sang Chul Lim1
Department of 1Otorhinolaryngology–Head and Neck Surgery, 2Internal Medicine, 3Pathology, Chonnam National
University Medical school, Hwasun Hospital
Introduction
Results
Conclusion
EGR-1 had abundant expression in human HNSCC tissue. EGR-1 knockdown
inhibited radiation-induced apoptosis through caspase 3, caspase, 7, PARP.
EGR-1 may play an important role in treatment response after radiation
therapy in human HNSCC.
Figure 4. Radiation upragulates EGR1 expression in human HNSCC. After 5Gy and 8Gy irradiation, mRNA and protein expression of
Egr1 increased with peak activation from 30 min to 2 h.
Figure 5. The activation of apoptosis related proteins after
radiation in human HNSCC cells. The cleaved caspase 3, cleaved
caspase 7, and cleaved PARP were increased at 2 h after irradiation in
SNU1041 and PCI50. pro-apoptotic protein Bax was also increased at 2 h
after irradiation in PCI50.
.
To investigate that the early growth response-1 (EGR1) expression in human
head and neck squamous cancer (HNSCC) and to evaluate whether EGR1
affects radiation-induced apoptosis and it would thus serves as the proper
prognostic biomolecular marker of radiation therapy in human HNSCC .
Aims
Summary
EGR1 have abundant expression in human hypopharyngeal cancer tissue
Radiation up-regulate EGR1 proteins in human HNSCC cell lines.
Radiation up-regulate apoptosis related proteins in human HNSCC cell
lines.
Knockdown of EGR1 inhibits radiation induced apoptosis in human HNSCC
cell line.
Knockdown of EGR1 inhibits the activation of apoptosis related proteins in
human HNSCC cell line.
Figure 6. The change of apoptosis related proteins by EGR1 knock down after radiation in human HNSCC cells. The cleaved
caspase 3, cleaved caspase 7, cleaved PARP activation was decreased, and XIAP activation was increased by EGR-1 knock down after irradiation
Figure 7. Effect of EGR1 on cell apoptosis after radiation in human HNSCC cells. EGR-1 knockdown (E) inhibited radiation-induced
apoptosis, compared with control cells (C) in cell apoptosis assay.
Table 1. Clinicopathologic variables of 28 patients with advanced hypopharyngeal cancer
Figure 1. Expression of EGR1 (A) Immunohistochemical stainig of Livin in human hypopharyngeal cancer tissues. Egr-1 immunoreactivity showed intense nuclear staining relative to adjacent tissue mucosa. (B) mRNA expression of EGR1 increased in tumor tissue compared with normal mucosa.
Figure 2. The survival curve according to EGR1 expression in human hypopharyngeal cancer - Mean duration of overall survival in the negative EGR1 group vs positive EGR1 group
: 41.4 months vs 53.6 months
The expression and function of EGR1
EGR1 over-expressed the variable cancer cells (esophagus, prostate, bladder, breast, stomach, colon) EGR1 is oncogene or tumor suppresser gene ?
- cancer progression, cell growth vs apoptosis ?
-ongogenic function in prostate cancer
- Positive prognostic effect on survival in nasopharyngeal cancer
Variables Value
Age (y): mean±SD (range) 63.18±7.91 (51-83)
Sex (male:female) 27:1
Location (piriform sinus:post. pharyngeal wall) 22:6
Stage (III : IV) 8:20
T stage (T1:T2:T3:T4) 1:14:6:7
N stage (N0:N1:N2) 2:10:16
Distant metastasis (M0:M1) 24:4
Tumor response after NC (CR,PR:NR) 27:1
Overall tumor response after CRT (CR:PR,NR) 22:6
Recurrence (no recur: recur) 10:12
3 year Overall survival (%) 46
A B *100
*200
Figure 3. EGR1 expression and knock down by siRNA in human head and neck squamous carcinoma cell lines
SNU 1041 PCI50
SNU 1041 PCI50
PCI50
No treatment
24hr after
5 cGy radiation
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