Expression and function of FRA2/JUND in cutaneous T-cell lymphomas.

Abstract

Adult T-cell leukemia/lymphoma (ATLL) and cutaneous T-cell lymphomas (CTCLs) are known to frequently express CC chemokine receptor 4 (CCR4). Previously, we investigated the transcriptional control of CCR4 expression in ATLL and have found that an activating protein 1 (AP1) family member, FBJ murine osteosarcoma viral oncogene homolog (FOS)-related antigen 2 (FRA2), is consistently expressed at high levels in ATLL and, together with v-JUN avian sarcoma virus 17 oncogene homolog D (JUND), up-regulates the expression of CCR4 as well as that of several proto-oncogenes such as v-MYB myeloblastosis viral oncogene homolog (MYB), murine double minute 2 homolog (MDM2), and B-cell lymphoma 6 (BCL6). Here, we examined the expression of these genes in clinical samples of CTCLs. We detected the transcripts of FRA2, JUND, CCR4, MYB, MDM2, and BCL6 at high levels in CTCL skin lesions. Except for BCL6, we confirmed protein expression of FRA2, JUND, CCR4, MYB, and MDM2 in CTCL skin lesions. Furthermore, siRNA-mediated knockdown of FRA2 or JUND suppressed cell growth and the expression of CCR4, MYB, MDM2, and BCL6 in CTCL cell lines. Our results, thus, demonstrate the presence of a common oncogenic cascade initiated by FRA2/JUND in CCR4-expressing mature T-cell malignancies such as ATLL and CTCLs.

• Authors: Takashi Nakayama, Tomonori Higuchi, Naoki Oiso, Akira Kawada, Osamu Yoshie
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 4 Pg. 1367-73 (Apr 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22493372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOSL2 protein, human
• Fos-Related Antigen-2
• JunD protein, human
• Proto-Oncogene Proteins c-jun

Topics

• Female
• Fos-Related Antigen-2 (genetics)
• Humans
• Lymphoma, T-Cell (genetics)
• Male
• Proto-Oncogene Proteins c-jun (genetics)
• Skin Neoplasms (genetics)