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Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

Rama AR, Hernandez R, Perazzoli G, Burgos M, Melguizo C, Vélez C, Prados J - Int J Mol Sci (2015)

Bottom Line: The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity.We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA.These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.

ABSTRACT
Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

No MeSH data available.


Related in: MedlinePlus

Transcriptional activity of CEA. Human CACO-2, HT29, HCT-116, SW480, RKO and T-84 colon adenocarcinoma cell lines, mice MC-38 colon cancer cell line, and the normal human colon CCD18co cell line Cells were co-transfected with luciferase expression vectors pPGL2/CEA or pGL2 and the Renilla expression vector CMV/Renilla. Luciferase activity of each transfection was normalized by the Renilla reading. Luciferase activity is represented by the ratio of the specific promoter over the activity of pGL2. Data represent the mean value of three replicates ± the standard error of the mean (SEM).
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ijms-16-12601-f001: Transcriptional activity of CEA. Human CACO-2, HT29, HCT-116, SW480, RKO and T-84 colon adenocarcinoma cell lines, mice MC-38 colon cancer cell line, and the normal human colon CCD18co cell line Cells were co-transfected with luciferase expression vectors pPGL2/CEA or pGL2 and the Renilla expression vector CMV/Renilla. Luciferase activity of each transfection was normalized by the Renilla reading. Luciferase activity is represented by the ratio of the specific promoter over the activity of pGL2. Data represent the mean value of three replicates ± the standard error of the mean (SEM).

Mentions: CEA activity was detected in all seven colon cancer cell lines by luciferase assay. Human HTC-116, CACO-2, RKO colon adenocarcinoma cell lines and mouse MC-38 colon cancer cells showed high levels of luciferase expression, whereas human HT-29, T-84 and SW480 adenocarcinoma cell lines showed a low degree of luciferase expression. Specifically, HTC-116 showed the highest level of luciferase among all of the colorectal cancer cells, while T-84 cells presented the least expression of cancer cells. In contrast, normal intestinal epithelial CCD18co cells demonstrated the lowest levels of CEA activity (Figure 1).


Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

Rama AR, Hernandez R, Perazzoli G, Burgos M, Melguizo C, Vélez C, Prados J - Int J Mol Sci (2015)

Transcriptional activity of CEA. Human CACO-2, HT29, HCT-116, SW480, RKO and T-84 colon adenocarcinoma cell lines, mice MC-38 colon cancer cell line, and the normal human colon CCD18co cell line Cells were co-transfected with luciferase expression vectors pPGL2/CEA or pGL2 and the Renilla expression vector CMV/Renilla. Luciferase activity of each transfection was normalized by the Renilla reading. Luciferase activity is represented by the ratio of the specific promoter over the activity of pGL2. Data represent the mean value of three replicates ± the standard error of the mean (SEM).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490463&req=5

ijms-16-12601-f001: Transcriptional activity of CEA. Human CACO-2, HT29, HCT-116, SW480, RKO and T-84 colon adenocarcinoma cell lines, mice MC-38 colon cancer cell line, and the normal human colon CCD18co cell line Cells were co-transfected with luciferase expression vectors pPGL2/CEA or pGL2 and the Renilla expression vector CMV/Renilla. Luciferase activity of each transfection was normalized by the Renilla reading. Luciferase activity is represented by the ratio of the specific promoter over the activity of pGL2. Data represent the mean value of three replicates ± the standard error of the mean (SEM).
Mentions: CEA activity was detected in all seven colon cancer cell lines by luciferase assay. Human HTC-116, CACO-2, RKO colon adenocarcinoma cell lines and mouse MC-38 colon cancer cells showed high levels of luciferase expression, whereas human HT-29, T-84 and SW480 adenocarcinoma cell lines showed a low degree of luciferase expression. Specifically, HTC-116 showed the highest level of luciferase among all of the colorectal cancer cells, while T-84 cells presented the least expression of cancer cells. In contrast, normal intestinal epithelial CCD18co cells demonstrated the lowest levels of CEA activity (Figure 1).

Bottom Line: The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity.We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA.These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.

ABSTRACT
Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

No MeSH data available.


Related in: MedlinePlus