MUC1 oncoprotein promotes growth and survival of human multiple myeloma cells

Kawano,Takeshi; Ahmad,Rehan; Nogi,Hiroko; Agata,Naoki; Anderson,Kenneth; Kufe,Donald

doi:10.3892/ijo.33.1.153

July 2008 Volume 33 Issue 1

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July 2008 Volume 33 Issue 1

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Article

MUC1 oncoprotein promotes growth and survival of human multiple myeloma cells

Authors:
- Takeshi Kawano
- Rehan Ahmad
- Hiroko Nogi
- Naoki Agata
- Kenneth Anderson
- Donald Kufe
View Affiliations / Copyright

Affiliations: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
Pages: 153-159
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Published online on: July 1, 2008

https://doi.org/10.3892/ijo.33.1.153
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Abstract

The MUC1 oncoprotein is aberrantly expressed in human multiple myeloma cells by mechanisms that are not understood. Moreover, the functional role of MUC1 in multiple myeloma is not known. The present studies demonstrate that the MUC1 gene locus is amplified in multiple myeloma cell lines and in primary cells from patients. The KMS28PE multiple myeloma cell line, which was found to have MUC1 gene amplification, was stably silenced for MUC1 using different siRNAs. Silencing MUC1 was associated with a decrease in nuclear β-catenin levels, consistent with the function of MUC1 in stabilizing β-catenin. MUC1 is also known to activate the IKKβ↷NF-κB pathway and KMS28PE cells silenced for MUC1 were found to have downregulation of IKKβ and IκBα phosphorylation, and decreased nuclear targeting of NF-κB p65. The results also demonstrate that MUC1: i) contributes to KMS28PE cell proliferation, and ii) protects against apoptosis and loss of self-renewal in the response to melphalan and dexamethasone. These findings indicate that MUC1 activates the β-catenin and NF-κB pathways in multiple myeloma cells and contributes to their growth and survival.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

MUC1 oncoprotein promotes growth and survival of human multiple myeloma cells

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