PT  - JOURNAL ARTICLE
AU  - TAKASHI NAKAYAMA
AU  - TOMONORI HIGUCHI
AU  - NAOKI OISO
AU  - AKIRA KAWADA
AU  - OSAMU YOSHIE
TI  - Expression and Function of <em>FRA2/JUND</em> in Cutaneous T-Cell Lymphomas
DP  - 2012 Apr 01
TA  - Anticancer Research
PG  - 1367--1373
VI  - 32
IP  - 4
4099  - http://ar.iiarjournals.org/content/32/4/1367.short
4100  - http://ar.iiarjournals.org/content/32/4/1367.full
SO  - Anticancer Res2012 Apr 01; 32
AB  - 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.