HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 20, 20607-20612, May 14, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/20/20607    most recent M310538200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raina, D. Articles by Kufe, D. Search for Related Content PubMed PubMed Citation Articles by Raina, D. Articles by Kufe, D. Social Bookmarking                      What's this?

The MUC1 Oncoprotein Activates the Anti-apoptotic Phosphoinositide 3-Kinase/Akt and Bcl-x_L Pathways in Rat 3Y1 Fibroblasts^*

Deepak Raina, Surender Kharbanda, and Donald Kufe¶

From the Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 and ILEX Products, Inc., Boston, Massachusetts 02215

The MUC1 transmembrane glycoprotein is overexpressed by most human carcinomas. Overexpression of MUC1 confers transformation; however, the signaling pathways activated by this oncoprotein are largely unknown. The present studies demonstrated that MUC1-induced transformation of 3Y1 fibroblasts is associated with increased levels of phospho-Akt and phospho-Bad. The finding that LY294002 blocks MUC1-mediated increases in phospho-Akt and phospho-Bad supports the involvement of phosphoinositide 3-kinase (PI3K) as an upstream effector of this response. We also show that MUC1 increases the expression of the anti-apoptotic Bcl-x_L protein (but not Bcl-2) by a PI3K-independent mechanism. In concert with these results, MUC1 attenuated (i) the loss of mitochondrial transmembrane potential, (ii) mitochondrial cytochrome c release, (iii) activation of caspase-9, and (iv) induction of apoptosis by the antimetabolite, 1--D-arabinofuranosylcytosine. Similar results were obtained with the anti-cancer agent, gemcitabine. These findings indicate that expression of MUC1 in 3Y1 cells activates the anti-apoptotic PI3K/Akt and Bcl-x_L pathways.

Received for publication, September 23, 2003 , and in revised form, March 2, 2004.

^* This work was supported by Grants CA29431 and CA97098 awarded by NCI, National Institutes of Health. D. K. has a financial interest in ILEX. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 617-632-3141; Fax: 617-632-2934; E-mail: donald_kufe{at}dfci.harvard.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Raina, R. Ahmad, M. D. Joshi, L. Yin, Z. Wu, T. Kawano, B. Vasir, D. Avigan, S. Kharbanda, and D. Kufe Direct Targeting of the Mucin 1 Oncoprotein Blocks Survival and Tumorigenicity of Human Breast Carcinoma Cells Cancer Res., June 15, 2009; 69(12): 5133 - 5141. [Abstract] [Full Text] [PDF]

				N. N. Khodarev, S. P. Pitroda, M. A. Beckett, D. M. MacDermed, L. Huang, D. W. Kufe, and R. R. Weichselbaum MUC1-Induced Transcriptional Programs Associated with Tumorigenesis Predict Outcome in Breast and Lung Cancer Cancer Res., April 1, 2009; 69(7): 2833 - 2837. [Abstract] [Full Text] [PDF]

				Q. Shen, J. J. Rahn, J. Zhang, N. Gunasekera, X. Sun, A. R.E. Shaw, M. J. Hendzel, P. Hoffman, A. Bernier, and J. C. Hugh MUC1 Initiates Src-CrkL-Rac1/Cdc42-Mediated Actin Cytoskeletal Protrusive Motility after Ligating Intercellular Adhesion Molecule-1 Mol. Cancer Res., April 1, 2008; 6(4): 555 - 567. [Abstract] [Full Text] [PDF]

				P. L. Beatty, S. E. Plevy, A. R. Sepulveda, and O. J. Finn Cutting Edge: Transgenic Expression of Human MUC1 in IL-10-/- Mice Accelerates Inflammatory Bowel Disease and Progression to Colon Cancer J. Immunol., July 15, 2007; 179(2): 735 - 739. [Abstract] [Full Text] [PDF]

				Y. Leng, C. Cao, J. Ren, L. Huang, D. Chen, M. Ito, and D. Kufe Nuclear Import of the MUC1-C Oncoprotein Is Mediated by Nucleoporin Nup62 J. Biol. Chem., July 6, 2007; 282(27): 19321 - 19330. [Abstract] [Full Text] [PDF]

				M. Siragusa, M. Zerilli, F. Iovino, M. G. Francipane, Y. Lombardo, L. Ricci-Vitiani, G. Di Gesu, M. Todaro, R. De Maria, and G. Stassi MUC1 Oncoprotein Promotes Refractoriness to Chemotherapy in Thyroid Cancer Cells Cancer Res., June 1, 2007; 67(11): 5522 - 5530. [Abstract] [Full Text] [PDF]

				L. Yin, S. Kharbanda, and D. Kufe Mucin 1 Oncoprotein Blocks Hypoxia-inducible Factor 1{alpha} Activation in a Survival Response to Hypoxia J. Biol. Chem., January 5, 2007; 282(1): 257 - 266. [Abstract] [Full Text] [PDF]

				H. Tsutsumida, B. J. Swanson, P. K. Singh, T. C. Caffrey, S. Kitajima, M. Goto, S. Yonezawa, and M. A. Hollingsworth RNA Interference Suppression of MUC1 Reduces the Growth Rate and Metastatic Phenotype of Human Pancreatic Cancer Cells. Clin. Cancer Res., May 15, 2006; 12(10): 2976 - 2987. [Abstract] [Full Text] [PDF]

				E. Andrian, D. Grenier, and M. Rouabhia Porphyromonas gingivalis-Epithelial Cell Interactions in Periodontitis Journal of Dental Research, May 1, 2006; 85(5): 392 - 403. [Abstract] [Full Text] [PDF]

				L. Huang, D. Chen, D. Liu, L. Yin, S. Kharbanda, and D. Kufe MUC1 Oncoprotein Blocks Glycogen Synthase Kinase 3{beta}-Mediated Phosphorylation and Degradation of {beta}-Catenin Cancer Res., November 15, 2005; 65(22): 10413 - 10422. [Abstract] [Full Text] [PDF]

				B. Vasir, D. Avigan, Z. Wu, K. Crawford, S. Turnquist, J. Ren, and D. Kufe Dendritic Cells Induce MUC1 Expression and Polarization on Human T Cells by an IL-7-Dependent Mechanism J. Immunol., February 15, 2005; 174(4): 2376 - 2386. [Abstract] [Full Text] [PDF]

				L. Yin, L. Huang, and D. Kufe MUC1 Oncoprotein Activates the FOXO3a Transcription Factor in a Survival Response to Oxidative Stress J. Biol. Chem., October 29, 2004; 279(44): 45721 - 45727. [Abstract] [Full Text] [PDF]