Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence

Caré, Alessandra; Silvani, Antonio; Meccia, Ettore; Mattia, Gianfranco; Peschle, Cesare; Colombo, Mario P.

doi:10.1038/sj.onc.1201875

Cited by 87 publications

(100 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Here we show that PLZF is expressed in melanocytes, but not in melanoma cells, a pattern that inversely correlates with that previously reported for HOXB7 (Care`et al, 1996(Care`et al, , 1998. Although we found a perfect PLZF DNA consensus sequence in HOXB7 promoter, we could not demonstrate its functional binding and no downregulation of HOXB7 mRNA was obtained through PLZF enforced expression.…”

Section: Introductionmentioning

confidence: 34%

Role of PLZF in melanoma progression

et al. 2004

Self Cite

View full text Add to dashboard Cite

The promyelocytic leukemia zinc finger (PLZF) protein has been described as a transcriptional repressor of homeobox (HOX)-containing genes during embryogenesis. As we previously demonstrated a functional link between overexpression of HOXB7 and melanoma progression, we investigated the lack of PLZF as the possible cause of HOXB7 constitutive activation in these neoplastic cells. Accordingly, we found PLZF expression in melanocytes, but not in melanoma cells, a pattern inversely related to that of HOXB7. PLZF retroviral gene transduction was then performed in a panel of melanoma cell lines, and tumorigenicity was compared with that of empty vector-transduced control cell lines. Evaluation of in vitro migration, invasion and adhesion indicated that PLZF gene transduction induced a less malignant phenotype, as confirmed through in vivo studies performed in athymic nude mice. This reduced tumorigenicity was not coupled with HOXB7 repression. In order to find more about the molecular targets of PLZF, the gene expression profiles of PLZF-and empty vector-transduced A375 melanoma cells were analysed by Atlas Cancer macroarray. Among several genes modulated by PLZF enforced expression, of particular interest were integrin avb3, osteonectin/SPARC and matrix metalloprotease-9 that were downmodulated, and the tyrosinase-related protein-1 that was upregulated in all the analysed samples. This profile confirms the reduced tumorigenic phenotype with reversion to a more differentiated, melanocyte like, pattern, thus suggesting a suppressor role for PLZF in solid tumors. Moreover, these results indicate that PLZF and HOXB7 are functionally independent and that their coupled deregulation may account for most of the alterations described in melanomas.

show abstract

Section: Introductionmentioning

confidence: 34%

Role of PLZF in melanoma progression

et al. 2004

Self Cite

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%

“…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]. In addition, HOXB7 overexpression may also regulate VEGF, IL-8 and Ang-2 by tumor cells [121].…”

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

“…14 and 17; and unpublished observations), cancer cell lines (40,41), and transient transfection assays using a variety of promoters (39,42). It will be interesting to examine the effects of the HOXB7 mutations presented here in these other biological systems.…”

Section: Figure 9 Ckii Phosphorylates Hoxb7 In Vitro (Autoradiogram)mentioning

confidence: 99%

Identification of Novel Functional Regions Important for the Activity of HOXB7 in Mammalian Cells

Yaron

McAdara

Lynch

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

Members of the HOX family of homeobox transcription factors play a role in pattern formation in diverse developmental systems. The clearly documented role of HOX genes in the proliferation and differentiation of primary hematopoietic cells and cell lines provides a convenient system to pursue a biochemical analysis of HOX gene function in mammalian cells. To explore the role of HOXB7 in myeloid hematopoiesis, a number of mutations and deletions in the gene were constructed that targeted sequences with known functions or in regions that had not been examined previously. The wild-type and mutant B7 constructs were introduced into the murine myelomonocytic cell line, 32D, and assayed for their effects on G-CSF-induced myeloid differentiation. Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation. A model proposing a role for these regions of HOXB7 is presented.

show abstract

Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence

Cited by 87 publications

References 14 publications

Role of PLZF in melanoma progression

Role of PLZF in melanoma progression

Angiogenesis and Multiple Myeloma

Identification of Novel Functional Regions Important for the Activity of HOXB7 in Mammalian Cells

Contact Info

Product

Resources

About