Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells.
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.
Bu
Xia
X
Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA.
Avraham
Hava Karsenty
HK
Li
Xiaoyu
X
Lim
Bing
B
Jiang
Shuxian
S
Fu
Yigong
Y
Pestell
Richard G
RG
Avraham
Shalom
S
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D016196:S Phase
C485646:KLHL2 protein, human; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016755:Proto-Oncogene Proteins c-jun; D019938:Cyclin D1
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