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The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.

Zhang Y, Molavi O, Su M, Lai R - BMC Cancer (2014)

Bottom Line: Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019).In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011).To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Shantou University Medical College, 22 Xinling Road, Shantou 515031, Guangdong Province, China. minsu@stu.edu.cn.

ABSTRACT

Background: Loss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied.

Methods: Using immunohistochemistry, we detected the STAT1 expression in a cohort of ESCC patients; In-vitro experiments, we used enforced gene transfection of STAT1C into two STAT1- weak/negative ESCC cell lines and siRNA knockdown of STAT1 in two STAT1-strong ESCC cell lines to detect STAT1 function in ESCC.

Results: We found that the expression of STAT1 was heterogeneous in ESCC, with 64 (49.0%) strongly positive cases, 59 (45.0%) weakly positive cases and 8 (6.1%) negative cases. STAT1 expression inversely correlated with the depth of tumor invasion and tumor size (p=0.047 and p=0.029, respectively, Chi square). Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019). In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011). Our in-vitro experiments revealed that STAT1 is proapoptotic and inhibitory to cell-cycle progression and colony formation. Lastly, we found evidence that STAT1 signaling in ESCC cells down-regulated the expression and/or activity of NF-κB and STAT3, both of which are known to have oncogenic potential.

Conclusion: To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC. Loss of STAT1, which is frequent in ESCC, contributes to the pathogenesis of these tumors.

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Expression of STAT1 and phospho-STAT1 in ESCC (n = 4) and esophageal immortalized cell lines (n = 4). ESCC cell lines included EC1, EC109, KYESE150 and KYSE510 and human esophageal immortalized cell lines included SHEE, NE2, NE3 and NE6. MCF7, a breast cancer cell line, served as a positive control. The expression of STAT1 was heterogeneous among these cell lines, and the expression of phospho-STAT1 was generally in parallel with the expression of STAT1.
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Fig2: Expression of STAT1 and phospho-STAT1 in ESCC (n = 4) and esophageal immortalized cell lines (n = 4). ESCC cell lines included EC1, EC109, KYESE150 and KYSE510 and human esophageal immortalized cell lines included SHEE, NE2, NE3 and NE6. MCF7, a breast cancer cell line, served as a positive control. The expression of STAT1 was heterogeneous among these cell lines, and the expression of phospho-STAT1 was generally in parallel with the expression of STAT1.

Mentions: In light of the clinical significance of STAT1 in ESCC, we examined its roles in ESCC using an in-vitro model. The expression of STAT1 in a cohort of human ESCC cell lines (EC1, EC109, KYSE150 and KYSE510) as well as a cohort of human immortalized esophageal epithelial cell lines (SHEE, NE2, NE3 and NE6) was examined using Western blots. MCF7, an estrogen receptor-positive breast cancer cell line, served as the positive control for STAT1. As shown in Figure 2, we were able to detect STAT1 in 6 of these 8 cell lines; EC109 and SHEE were STAT1-negative. In the 6 STAT1-positive cell lines, EC1 and KYSE150 expressed STAT1 relatively weakly, whereas KYSE510, NE2, NE3 and NE6 expressed STAT1 relatively strongly. The expression of the phosphorylated/activated form of STAT1 (p-STAT1) in these cell lines was also assessed in these 8 cell lines. Except for EC1, all STAT1-positive cell lines expressed p-STAT1, although all of the immortalized cell lines (including NE2, NE3 and NE6) expressed p-STAT1 relatively weakly.Figure 2


The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.

Zhang Y, Molavi O, Su M, Lai R - BMC Cancer (2014)

Expression of STAT1 and phospho-STAT1 in ESCC (n = 4) and esophageal immortalized cell lines (n = 4). ESCC cell lines included EC1, EC109, KYESE150 and KYSE510 and human esophageal immortalized cell lines included SHEE, NE2, NE3 and NE6. MCF7, a breast cancer cell line, served as a positive control. The expression of STAT1 was heterogeneous among these cell lines, and the expression of phospho-STAT1 was generally in parallel with the expression of STAT1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4233059&req=5

Fig2: Expression of STAT1 and phospho-STAT1 in ESCC (n = 4) and esophageal immortalized cell lines (n = 4). ESCC cell lines included EC1, EC109, KYESE150 and KYSE510 and human esophageal immortalized cell lines included SHEE, NE2, NE3 and NE6. MCF7, a breast cancer cell line, served as a positive control. The expression of STAT1 was heterogeneous among these cell lines, and the expression of phospho-STAT1 was generally in parallel with the expression of STAT1.
Mentions: In light of the clinical significance of STAT1 in ESCC, we examined its roles in ESCC using an in-vitro model. The expression of STAT1 in a cohort of human ESCC cell lines (EC1, EC109, KYSE150 and KYSE510) as well as a cohort of human immortalized esophageal epithelial cell lines (SHEE, NE2, NE3 and NE6) was examined using Western blots. MCF7, an estrogen receptor-positive breast cancer cell line, served as the positive control for STAT1. As shown in Figure 2, we were able to detect STAT1 in 6 of these 8 cell lines; EC109 and SHEE were STAT1-negative. In the 6 STAT1-positive cell lines, EC1 and KYSE150 expressed STAT1 relatively weakly, whereas KYSE510, NE2, NE3 and NE6 expressed STAT1 relatively strongly. The expression of the phosphorylated/activated form of STAT1 (p-STAT1) in these cell lines was also assessed in these 8 cell lines. Except for EC1, all STAT1-positive cell lines expressed p-STAT1, although all of the immortalized cell lines (including NE2, NE3 and NE6) expressed p-STAT1 relatively weakly.Figure 2

Bottom Line: Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019).In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011).To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Shantou University Medical College, 22 Xinling Road, Shantou 515031, Guangdong Province, China. minsu@stu.edu.cn.

ABSTRACT

Background: Loss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied.

Methods: Using immunohistochemistry, we detected the STAT1 expression in a cohort of ESCC patients; In-vitro experiments, we used enforced gene transfection of STAT1C into two STAT1- weak/negative ESCC cell lines and siRNA knockdown of STAT1 in two STAT1-strong ESCC cell lines to detect STAT1 function in ESCC.

Results: We found that the expression of STAT1 was heterogeneous in ESCC, with 64 (49.0%) strongly positive cases, 59 (45.0%) weakly positive cases and 8 (6.1%) negative cases. STAT1 expression inversely correlated with the depth of tumor invasion and tumor size (p=0.047 and p=0.029, respectively, Chi square). Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019). In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011). Our in-vitro experiments revealed that STAT1 is proapoptotic and inhibitory to cell-cycle progression and colony formation. Lastly, we found evidence that STAT1 signaling in ESCC cells down-regulated the expression and/or activity of NF-κB and STAT3, both of which are known to have oncogenic potential.

Conclusion: To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC. Loss of STAT1, which is frequent in ESCC, contributes to the pathogenesis of these tumors.

Show MeSH
Related in: MedlinePlus