HOXC5 and HOXC8 Expression Are Selectively Turned on in Human Cervical Cancer Cells Compared to Normal Keratinocytes

Alami, Younes; Castronovo, Vincent; Belotti, Dorina; Flagiello, Domenico; Clausse, Nathalie

doi:10.1006/bbrc.1999.0516

Cited by 70 publications

(74 citation statements)

References 28 publications

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“…Thus, in recent years, much effort has been devoted to the study of HOX genes and proteins and their link with cancer (Shah and Sukumar, 2010). In cervix, despite some evidences of HOX member modulation (Alami et al, 1999;Hung et al, 2003;Lopez et al, 2006b;Gonzalez-Herrera et al, 2015), the participation of these transcription factors in cervical carcinogenesis has not been explored in depth. In this work, we evaluated HOX gene deregulation in CC; in particular, we focused on HOXA9 modulation and whether this phenomenon results in an advantage for the CC cell.…”

Section: Introductionmentioning

confidence: 99%

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Alvarado-Ruíz¹,

Martínez-Silva²,

Torres-Reyes³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with nontumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CCderived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.

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Section: Introductionmentioning

confidence: 99%

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Alvarado-Ruíz¹,

Martínez-Silva²,

Torres-Reyes³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…Among these, in the gynecological field, small numbers of studies have been reported. Alami et al 29 reported that the vast majority of HOX genes were expressed in normal cervical keratinocytes, but only HOXA2, A7, C5, C8 and D12 were silent. They observed that this pattern was conserved in the SiHa cervical carcinoma cell line, except for the appearance of HOXC5 and C8 mRNA, and suggested that HOXC5 and/or HOXC8 could be involved in the process leading to the oncogenic transformation of cervical keratinocytes.…”

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confidence: 99%

Expression pattern of the class I homeobox genes in ovarian carcinoma

et al. 2010

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Objective: Although some sporadic reports reveal the link between the homeobox (HOX) genes and ovarian carcinoma, there is no comprehensive analysis of the expression pattern of the class I homeobox genes in ovarian carcinoma that determines the candidate genes involved in ovarian carcinogenesis. Methods: The different patterns of expression of 36 HOX genes were analyzed, including 4 ovarian cancer cell lines and 4 normal ovarian tissues. Using a reverse transcription-polymerase chain reaction (RT-PCR) and quantification analysis, the specific gene that showed a significantly higher expression in ovarian cancer cell lines than in normal ovaries was selected, and western blot analysis was performed adding 7 ovarian cancer tissue specimens. Finally, immunohistochemical and immunocytochemical analyses were performed to compare the pattern of expression of the specific HOX gene between ovarian cancer tissue and normal ovaries. Results: Among 36 genes, 11 genes had a different level of mRNA expression between the cancer cell lines and the normal ovarian tissues. Of the 11 genes, only HOXB4 had a significantly higher level of expression in ovarian cancer cell lines than in normal ovaries (p=0.029). Based on western blot, immunohistochemical, and immunocytochemical analyses, HOXB4 was expressed exclusively in the ovarian cancer cell lines or cancer tissue specimens, but not in the normal ovaries. Conclusion:We suggest HOXB4 may be a novel candidate gene involved in ovarian carcinogenesis.

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“…Expression of Hoxc8 correlates with higher Gleason grades in prostate tumors, and the overexpression of Hoxc8 can suppress androgen-dependent transcription in prostate cancer cells (15,16). It is selectively activated in cervical cancer cells (17) and expressed only in esophageal squamous cell carcinoma tissue, but not in noncancerous mucosa (18).…”

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confidence: 99%

Identification of aHoxc8-regulated transcriptional network in mouse embryo fibroblast cells

Lei

Juan

Kim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The transcription factor, Hoxc8, is a member of the homeobox gene family that is vital for growth and differentiation. Previously, we identified 34 genes whose expression levels were changed at least 2-fold by forced expression of Hoxc8 in C57BL͞6J mouse embryo fibroblast cells using a mouse 16,463-gene oligonucleotide microarray. In the present study, we used the combined power of microarray profiling, global Hoxc8 DNA-binding site analysis, and high-throughput chromatin immunoprecipitation assays to identify direct and biologically relevant targets of Hoxc8 in vivo. Here we show that 19 of the 34 responsive genes contain Hoxc8 consensus DNA-binding sequence(s) in their regulatory regions. Chromatin immunoprecipitation analysis indicated that Hoxc8-DNA interaction was detected in five of the 19 candidate genes. All of these five target genes have been implicated in oncogenesis, cell adhesion, proliferation, and apoptosis. Overall, the genes described here should aid in the understanding of global regulatory networks of Hox genes and to provide valuable insight into the molecular basis of Hoxc8 in development and carcinogenesis.cancer ͉ chromatin immunoprecipitation ͉ Hox protein binding sites ͉ microarray

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HOXC5 and HOXC8 Expression Are Selectively Turned on in Human Cervical Cancer Cells Compared to Normal Keratinocytes

Cited by 70 publications

References 28 publications

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Expression pattern of the class I homeobox genes in ovarian carcinoma

Identification of aHoxc8-regulated transcriptional network in mouse embryo fibroblast cells

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