Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells

Simeone, Antonio; Acampora, Dario; Nigro, Vincenzo; Faiella, A.; D’Esposito, Maurizio; Stornaiuolo, Anna; Mavilio, Fulvio; Boncinelli, Edoardo

doi:10.1016/0925-4773(91)90029-6

Cited by 277 publications

(159 citation statements)

References 62 publications

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“…These regions are characterized by the presence of multiple positive and negative regulatory elements including retinoic acid-responsive sites. It has been shown that the retinoic acidinduced expression of silent HOX genes proceeded in a sequential order: the 3'-end HOX genes respond earlier than the 5'-end HOX genes [9,10]. Similar sequential responses were observed after inhibition of the HOX gene expression by antisense oligodeoxynucleotides [11].…”

Section: Introductionmentioning

confidence: 78%

Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers

et al. 1996

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The expression pattern of the HOXB gene cluster in four xenografted small-cell lung cancers was compared to the methylation of the DNA in the corresponding genomic regions. In 90% (17/19) of the studied cases, the expressed genes were in methylated regions whereas 70% (12/17) of the unexpressed genes were in unmethylated regions. This specific behavior could correspond to a particular gene expression regulation mechanism of the HOX gene network. Since some genes (HOXB2, HOXB4, HOXB7) were always inactive when unmethylated, this unexpected relationship might indicate their key function(s) in the HOX gene network.

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Section: Introductionmentioning

confidence: 78%

Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers

et al. 1996

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“…In human embryonic carcinoma cells, HOX4C is not affected by retinoic acid stimulation, but other HOX genes, i.e., HOX4D, HOX4F, HOX4H, and HOX41, are suppressed (38). This evidence suggests that HOX4C plays a distinct role in the initiation of limb formation.…”

Section: Discussionmentioning

confidence: 96%

Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts

Xue

Hasunuma

Asahara

et al. 1997

Arthritis & Rheumatism

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Objective. To examine the expression of genes of the HOX D cluster in the synovial tissue of patients with rheumatoid arthritis (RA), and to determine whether basic fibroblast growth factor (bFGF) influences the expression and transcriptional regulation of the gene.Methods. The expression of genes of the HOX D cluster, including HOX4C, HOX4D, HOX4H, and HOX41, was determined in the synovium of 4 patients with RA and 4 with osteoarthritis (OA) by in situ reverse transcription (RT) and RT-polymerase chain reaction (RT-PCR). The induction of HOX4C messenger RNA (mRNA) by bFGF was determined by RT-PCR. The binding activity of a transcriptional regulator of the HOX4C gene, C2, was analyzed by the mobility shift assay. NIH-3T3 cells transfected with a construct containing C2 binding sequence were incubated with bFGF, and the activity of the reporter was measured by luciferase assay.Results. Using an in situ RT assay, specific expression of HOX4C mRNA was detected in 3 of 4 RA synovial samples, whereas none of the OA synovia expressed HOX4C. HOX4D, HOX4H, and HOX41 genes were expressed in all synovial samples from RA and OA

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“…This original observation may allow a better understanding of the crucial role played by this HOX gene in breast cancer cells. Indeed, whereas it was clearly demonstrated that HOXA1 gene is a primary target for retinoic acid in distinct cell types such as embryonal carcinoma cells (26) and breast cancer cells, no information was available about possible HOX modulation by steroids. A recent study reported that expression of two murine Hox genes could respond to hormonal secretions (27).…”

Section: Hoxa1 Is Modulated By Progestin Org 2058 In Mcf7 Cellsmentioning

confidence: 99%

Detection of HOXA1 Expression in Human Breast Cancer

Chariot

Castronovo

1996

Biochemical and Biophysical Research Communications

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Homeodomain-containing proteins are transcription factors that regulate the coordinated expression of multiple genes involved in development, differentiation and malignant transformation. To better understand the role played by these proteins in breast cancer cells, we demonstrate, using semi-quantitative RT-PCR experiments, that progestin induces HOXA1 mRNAs in MCF7 cells. This is the first evidence of regulation of a HOX gene by steroids. Moreover, we detected HOXA1 expression in a variety of human breast cancer lesions, suggesting that HOXA1 may be required for the establishment of breast cancer cells phenotype. We propose that HOXA1 gene could be one of the orchestrators that regulate breast epithelial cell differentiation and that alteration of HOXA1 expression could play a role in breast cancer progression. © 1996 Academic Press, Inc.Cell transformation and tumor progression are associated with coordinated activation an inhibition of specific intact or altered genes (1,2). This complex genetic program involves proteins that control cellular proliferation and/or differentiation. Transcription factors implicated in organogenesis are ideal candidates to regulate these multistep processes.Homeodomain-containing proteins act, as transcription factors, in the genetic control of genes involved in development and differentiation (3). These genes were initially discovered in Drosophila where they control segment identity (4). Homologous homeobox genes have been since cloned in multiple species, including human (5,6). To date, 38 human class I homeobox genes have been discovered. They are organized in four clusters (HOX loci A, B, C and D), located respectively on chromosomes 7, 17, 12 and 2 (7).There is accumulating evidence suggesting a possible involvement of HOX genes in malignant transformation. A potential role of these genes in neoplasia was first documented in leukemia, as reviewed (8). Distinct chromosomal translocations or incorporation of a regulatory element in the vicinity of a homeobox gene confers an oncogenic potential to the protein product in hematopoietic cells (9,11). Moreover, alterations of HOX expression have been also detected in a variety of human tumors (12-15). In addition, ectopic HOX expression obtained by transfections of Hox genes into murine and rat cells induces tumorigenicity (16). This oncogenic potential has also been attributed to divergent homeobox genes that are not included in the 4 clusters (17)(18)(19)(20).As a first step to investigate the role played by HOX genes in breast cancer cells, we have previously cloned three alternatively spliced HOXA1 transcripts from a MCF7 cDNA library and demonstrated that HOXA1 expression was modulated by retinoic acid in these cells (21). In this study, we further demonstrate that these HOXA1 transcripts are induced by progestins, another differentiating agent, in MCF7 cells. Moreover, we systematically detected HOXA1 expression in a variety of human breast cancer lesions as well as in the adjacent tissues. Taken together, our results sugge...

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Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells

Cited by 277 publications

References 62 publications

Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers

Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers

Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts

Detection of HOXA1 Expression in Human Breast Cancer

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