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Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells

Abstract

Mayven is a member of the kelch-related superfamily of proteins, characterized by a series of ‘kelch’ repeats at their carboxyl terminus and a BTB/POZ domain at their NH2-terminus. Little is known about the role of Mayven in cancer. Here, we report that Mayven expression was abundant and diffuse in primary human epithelial breast tumor cells as compared to normal breast epithelial cells, where Mayven was detected in the normal breast layer of the mammary ducts. Overexpression of Mayven resulted in an induction of c-Jun protein levels, as well as increased AP-1 (activating protein 1) transcriptional activity in MCF-7 and T47D breast cancer cells through its BTB/POZ domain. Furthermore, Mayven activated c-Jun N-terminal kinase in breast cancer cells. Mayven, through its BTB/POZ domain, induced cyclin D1 expression and cyclin D1 promoter activity and promoted cell cycle progression from the G1 to S phase. MCF-7 cells transduced with the recombinant retroviral sense Mayven (pMIG-W-Mayven) showed significant induction of c-Jun and cyclin D1 mRNA expression and activities as compared to the retroviral vector alone, while MCF-7 cells transduced by the recombinant retroviral antisense Mayven (pMIG-W-Mayven-AS) demonstrated a significant decrease in c-Jun and cyclin D1 expression and activities. Given the crucial functions of cyclin D1 and AP-1 signaling in oncogenesis, our results strongly suggest that overexpression of Mayven may promote tumor growth through c-Jun and cyclin D1.

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Abbreviations

APL:

acute promyelocytic leukemia

bZIP:

basic region-leucine zipper

JNK:

c-Jun N-terminal kinase

EB:

ethidium bromide

HIC-1:

hypermethylated in cancer

Krp1:

kelch-related protein 1

MAP:

mitogen-activated protein

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Acknowledgements

We thank Mikyung Kim, Heather Kil and Sarah Evans for typing the manuscript and Janet Delahanty for editing of the manuscript. This work was supported in part by the National Institutes of Health Grant 1R01 CA096805 (HA), a K18 Career Enhancement Award (PAR-02-069) (HA), he Susan G Komen Breast Cancer Foundation Award (SA), the Department of Army Concept Awards (SA and HA) and NIH Grant 1R01 HL080699 (SA). This paper is dedicated to Charlene Engelhard and Ronald Ansin for their continuing and HA friendship and support for our research program.

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Correspondence to Shalom Avraham.

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Bu, X., Avraham, H., Li, X. et al. Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells. Oncogene 24, 2398–2409 (2005). https://doi.org/10.1038/sj.onc.1208466

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