HOXB7 Constitutively Activates Basic Fibroblast Growth Factor in Melanomas

Caré, Alessandra; Silvani, Anna; Meccia, Ettore; Mattia, Gianfranco; Stoppacciaro, Antonella; Parmiani, Giorgio; Peschle, Cesare; Colombo, Mario P.

doi:10.1128/mcb.16.9.4842

Cited by 192 publications

(193 citation statements)

References 47 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…The putative Hox gene targets may thus include growth factors, their receptors, and molecules involved in post-receptor signaling. Consistent with this possibility, basic ®broblast growth factor production was detected in HOXB7 over-expressing melanoma cells (Care et al, 1996). The Hoxb4-transduced Rat-1 or FDC-P1 cells produced no bioactive substance(s) detectable by proliferation assays (E Kroon and JK, data not shown).…”

Section: Discussionmentioning

confidence: 66%

Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1

et al. 1998

View full text Add to dashboard Cite

The products of PBX homeobox genes, which were initially discovered in reciprocal translocations occurring in human leukemias, have been shown to cooperate in the in vitro DNA binding with HOX proteins. Despite the growing body of data implicating Hox genes in the development of various cancers, little is known about the role of HOX ± PBX interactions in the regulation of proliferation and induction of transformation of mammalian cells. We build on the existing model of Hoxinduced transformation of Rat-1 cells to show that both cellular transformation and proliferation induced by Hoxb4 and Hoxb3 are greatly modulated by the levels of available PBX1 present in these cells. Furthermore, we show that the transforming capacity of these two HOX proteins depends on their conserved tetrapeptide and homeodomain regions which mediate binding to PBX and DNA, respectively. Taken together, results of this study demonstrate that cooperation between HOX and PBX proteins modulates cellular proliferation and strongly suggest that cooperative DNA binding by these two groups of proteins represent the basis for Hoxinduced cellular transformation.

show abstract

Section: Discussionmentioning

confidence: 66%

Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1

et al. 1998

View full text Add to dashboard Cite

show abstract

“…The deregulation of the homeobox (HOX) B genes has been previously correlated to the angiogenic process as well as to tumoral-induced neoangiogenesis and tumor progression in solid cancer [120][121][122][123]. Particularly, the overexpression of HOXB7 has been associated with the tumor-related angiogenic switch, cell proliferation, and the production of bFGF by breast cancer and melanoma cells [122,123].…”

Section: Genes Involved In the Regulation Of The Pro-angiogenic Profimentioning

confidence: 99%

Angiogenesis and Multiple Myeloma

Giuliani

Storti

Bolzoni

et al. 2011

Cancer Microenvironment

View full text Add to dashboard Cite

The bone marrow microenvironment in multiple myeloma is characterized by an increased microvessel density. The production of pro-angiogenic molecules is increased and the production of angiogenic inhibitors is suppressed, leading to an "angiogenic switch". Here we present an overview of the role of angiogenesis in multiple myeloma, the pro-angiogenic factors produced by myeloma cells and the microenvironment, and the mechanisms involved in the myeloma-induced angiogenic switch. Current data suggest that the increased bone marrow angiogenesis in multiple myeloma is due to the aberrant expression of angiogenic factors by myeloma cells, the subsequent increase in pro-angiogenic activity of normal plasma cells as a result of myeloma cell angiogenic activity, and the increased number of plasma cells overall. Hypoxia also contributes to the angiogenic properties of the myeloma marrow microenvironment. The transcription factor hypoxia-inducible factor-1α is overexpressed by myeloma cells and affects their transcriptional and angiogenic profiles. In addition, potential roles of the tumor suppressor gene inhibitor of growth family member 4 and homeobox B7 have also been recently highlighted as repressors of angiogenesis and pro-angiogenic related genes, respectively. This complex pathogenetic model of myeloma-induced angiogenesis suggests that several proangiogenic molecules and related genes in myeloma cells and the microenvironment are potential therapeutic targets.

show abstract

“…The PBX1 gene was first identified as an oncogenic fusion between the PBX homeodomain and the activation domain of the E2A gene product (Kamps et al, 1990;Nourse et al, 1990). Currently however, the regulatory regions of the few downstream targets for HOX proteins, including targets such as p21 (Bromleigh and Freedman, 2000), p53 (Raman et al, 2000a), the progesterone receptor (Raman et al, 2000b), or FGF (Care et al, 1996), do not appear to contain PBX-HOX binding sites. Another level of regulation appears to be the finding that localization of the putative cofactor PBX/EXD proteins to the nucleus is dependent on complex formation with MEIS/HTH homeodomain proteins (Abu-Shaar et al, 1999;Berthelsen et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

Kömüves

Michael

Arbeit

et al. 2002

Developmental Dynamics

View full text Add to dashboard Cite

The HOX homeodomain proteins are fundamental regulators of organ and tissue development, where they are thought to function as transcription factors, and HOX gene expression has been associated with numerous types of cancers. Previous studies have demonstrated that enforced expression of the HOXB4 protein transforms cultured fibroblasts and leads to a selective expansion of the hematopoietic stem cell pool, suggesting that this protein might play a role in cellular proliferation. In support of this concept, we now show that enforced expression of HOXB4 in human neonatal keratinocytes results in increased cellular proliferation and colony formation as well as decreased expression of the alpha-2-integrin and CD44 cell surface adhesion molecules. We previously have reported HOXB4 gene expression in the basal and suprabasal layers of developing human skin and now show extensive HOXB4 mRNA in psoriatic skin and basal cell carcinoma. In fetal human skin HOXB4 protein expression was both nuclear and cytoplasmic within epidermal basal cells and in hair follicle inner and outer root sheath cells, whereas strong nuclear signals were observed in the bulge region. In adult skin, HOXB4 protein expression was both nuclear and cytoplasmic, but was predominantly localized to the intermediate and differentiated cell layers. In contrast to the striking gradient patterns of HOX gene and protein expression previously described in developing spinal cord and limb, HOXB4 protein was uniformly detected in all regions of the fetal and adult skin. Although little HOXB4 signal localized to proliferative cell layers, as marked by proliferating cell nuclear antigen (PCNA) staining, in normal adult epidermis, nuclear HOXB4 protein expression substantially overlapped with PCNA-positive cell in a series of samples of hyperproliferative skin. Taken together, these data suggest that nuclear HOXB4 protein may play a role in the regulation of cellular proliferation/adhesion in developing fetal human epidermis and in hyperproliferation conditions, including cancers, in adult epidermis.Published 2002 Wiley-Liss, Inc. †

show abstract

HOXB7 Constitutively Activates Basic Fibroblast Growth Factor in Melanomas

Cited by 192 publications

References 47 publications

Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1

Cellular proliferation and transformation induced by HOXB4 and HOXB3 proteins involves cooperation with PBX1

Angiogenesis and Multiple Myeloma

HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

Contact Info

Product

Resources

About