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Overexpression of Eag1 potassium channels in clinical tumours.

Hemmerlein B, Weseloh RM, Mello de Queiroz F, Knötgen H, Sánchez A, Rubio ME, Martin S, Schliephacke T, Jenke M - Mol. Cancer (2006)

Bottom Line: The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body.Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation.Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Georg-August University, Göttingen, Germany. hemmer@med.uni-goettingen.de

ABSTRACT

Background: Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1) are associated with the production of tumours in patients and in animals. We have now studied the expression pattern of the Eag1 channel in a large range of normal and tumour tissues from different collections utilising molecular biological and immunohistochemical techniques.

Results: The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body. Tumour samples, however, showed a significant overexpression of the channel with high frequency (up to 80% depending on the tissue source) regardless of the detection method (staining with either one of the antibodies, or detection of Eag1 RNA).

Conclusion: Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation. Eag1 may therefore represent a promising target for the tailored treatment of human tumours. Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects.

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Representative images of neoplastic tissue: Immunoperoxidase stainings using Eag1.62mAb as primary antibody. Examples of high expression levels of Eag1 in mammary carcinoma (a), prostate carcinoma (b), hepatocellular carcinomas (c) colon carcinoma (d) or squamous cell lung carcinoma (e) (Hematoxylin counterstain, ×400).
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Figure 5: Representative images of neoplastic tissue: Immunoperoxidase stainings using Eag1.62mAb as primary antibody. Examples of high expression levels of Eag1 in mammary carcinoma (a), prostate carcinoma (b), hepatocellular carcinomas (c) colon carcinoma (d) or squamous cell lung carcinoma (e) (Hematoxylin counterstain, ×400).

Mentions: Immunohistochemical analysis applied to a larger number of breast carcinomas further completed and confirmed the previous RT-PCR results. Seven of eight specimens in our archive were unequivocally positive for Eag1 albeit to varying degrees. We also tested a commercial multiple tissue array containing samples from 50 breast cancer cases- all were clearly positive with Eag1 being detectable in a large proportion of the tumour cells. Additionally, we studied tumour samples from the Manitoba Breast Tumor Bank, with similar results. In contrast, the mammary epithelium was negative under both normal conditions and in the tumour-free areas in all cases. Altogether, Eag1 could be detected in 80% of the breast cancers investigated in this study (Table 1, Figures 5 and 6). We also analyzed other common human tumours with comparable results. The immunohistochemical data on tumour samples are summarised in Table 1.


Overexpression of Eag1 potassium channels in clinical tumours.

Hemmerlein B, Weseloh RM, Mello de Queiroz F, Knötgen H, Sánchez A, Rubio ME, Martin S, Schliephacke T, Jenke M - Mol. Cancer (2006)

Representative images of neoplastic tissue: Immunoperoxidase stainings using Eag1.62mAb as primary antibody. Examples of high expression levels of Eag1 in mammary carcinoma (a), prostate carcinoma (b), hepatocellular carcinomas (c) colon carcinoma (d) or squamous cell lung carcinoma (e) (Hematoxylin counterstain, ×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1621079&req=5

Figure 5: Representative images of neoplastic tissue: Immunoperoxidase stainings using Eag1.62mAb as primary antibody. Examples of high expression levels of Eag1 in mammary carcinoma (a), prostate carcinoma (b), hepatocellular carcinomas (c) colon carcinoma (d) or squamous cell lung carcinoma (e) (Hematoxylin counterstain, ×400).
Mentions: Immunohistochemical analysis applied to a larger number of breast carcinomas further completed and confirmed the previous RT-PCR results. Seven of eight specimens in our archive were unequivocally positive for Eag1 albeit to varying degrees. We also tested a commercial multiple tissue array containing samples from 50 breast cancer cases- all were clearly positive with Eag1 being detectable in a large proportion of the tumour cells. Additionally, we studied tumour samples from the Manitoba Breast Tumor Bank, with similar results. In contrast, the mammary epithelium was negative under both normal conditions and in the tumour-free areas in all cases. Altogether, Eag1 could be detected in 80% of the breast cancers investigated in this study (Table 1, Figures 5 and 6). We also analyzed other common human tumours with comparable results. The immunohistochemical data on tumour samples are summarised in Table 1.

Bottom Line: The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body.Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation.Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Georg-August University, Göttingen, Germany. hemmer@med.uni-goettingen.de

ABSTRACT

Background: Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1) are associated with the production of tumours in patients and in animals. We have now studied the expression pattern of the Eag1 channel in a large range of normal and tumour tissues from different collections utilising molecular biological and immunohistochemical techniques.

Results: The use of reverse transcription real-time PCR and specifically generated monoclonal anti-Eag1 antibodies showed that expression of the channel is normally limited to specific areas of the brain and to restricted cell populations throughout the body. Tumour samples, however, showed a significant overexpression of the channel with high frequency (up to 80% depending on the tissue source) regardless of the detection method (staining with either one of the antibodies, or detection of Eag1 RNA).

Conclusion: Inhibition of Eag1 expression in tumour cell lines reduced cell proliferation. Eag1 may therefore represent a promising target for the tailored treatment of human tumours. Furthermore, as normal cells expressing Eag1 are either protected by the blood-brain barrier or represent the terminal stage of normal differentiation, Eag1 based therapies could produce only minor side effects.

Show MeSH
Related in: MedlinePlus