Pre-B-cell leukemia transcription factor 1 is a major target of promyelocytic leukemia zinc-finger-mediated melanoma cell growth suppression

Abstract

Promyelocytic leukemia zinc-finger (PLZF) is a transcriptional repressor and tumor suppressor. PLZF is expressed in melanocytes but not in melanoma cells, and recovery of PLZF expression markedly suppresses melanoma cell growth. Several target genes regulated by PLZF have been identified, but the precise function of PLZF remains uncertain. Here, we searched for candidate target genes of PLZF by DNA microarray analysis. Pre-B-cell leukemia transcription factor 1 (Pbx1) was one of the prominently suppressed genes. Pbx1 was highly expressed in melanoma cells, and its expression was reduced by transduction with the PLZF gene. Moreover, the growth suppression mediated by PLZF was reversed by enforced expression of Pbx1. Knockdown of Pbx1 by specific small interfering RNAs suppressed melanoma cell growth. We also found that Pbx1 binds HoxB7. Reverse transcription-polymerase chain reaction analysis demonstrated that repression of Pbx1 by PLZF reduces the expression of HoxB7 target genes, including tumor-associated neoangiogenesis factors such as basic fibroblast growth factor, angiopoietin-2 and matrix metalloprotease 9. These findings suggest that deregulation of Pbx1 expression owing to loss of PLZF expression contributes to the progression and/or pathogenesis of melanoma.

PLZF Induces the Spontaneous Acquisition of Memory/Effector Functions in T Cells Independently of NKT Cell-Related Signals

“…Furthermore, NKT cells are not dependent on PLZF to undergo proliferation, as has been shown in PLZF-deficient mice (16,17). Indeed, PLZF has been reported to inhibit cell cycle progression (45,46) and to cause cell quiescence (47) and suppression of cell growth (48). Therefore, it is possible that the NKT cell proliferative burst is actually dependent on the rapid downregulation of PLZF that we reported (16).…”

Ovarian Cancer Chemoresistance Relies on the Stem Cell Reprogramming Factor PBX1

“…Besides hematopoietic malignancy, PBX1 is also highly expressed in solid tumors including melanoma, prostate, ovarian, and breast cancers (23)(24)(25). In ovarian cancer, PBX1 has been identified as an effector in the NOTCH3 signaling pathway, which is known to maintain stemness and promote platinum drug resistance in ovarian cancer cells (10,26).…”

Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells

“…On the other hand, we found that enforced expression of Pbx1 alone was not sufficient to restore the decreased colony-forming capacity of Evi-1 À/À P-Sp cells (data not shown). These Pbx1 has also been implicated in the development of several tumors including hematological malignancies (Kamps et al, 1990(Kamps et al, , 1991Nourse et al, 1990;Qiu et al, Shiraishi et al, 2007;Park et al, 2008). It is required for the execution of some Hox-dependent block of differentiation, and/or transformation (Krosl et al, 1998;Knoepfler et al, 2001;Yaron et al, 2001), and mutations of HoxA9 that prevent interaction with Pbx proteins abrogate its oncogenic properties (Schnabel et al, 2000).…”