<i>Homeobox</i> gene expression and mutation in cervical carcinoma cells

Hung, Yao Ching; Ueda, Masatsugu; Terai, Yoshito; Kumagai, Koji; Ueki, Ken; Kanda, Koji; Yamaguchi, Hiroyuki; Akise, Daisuke; Ueki, Minoru

doi:10.1111/j.1349-7006.2003.tb01461.x

Cited by 45 publications

(39 citation statements)

References 27 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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“…Currently, in gynecological field, there have been several reports suggesting that the abnormal expression of particular HOX genes is associated with cervical, ovarian, and endometrial cancers. [16][17][18][19] As for the cervical cancers, several studies have shown a different pattern of expression of specific HOX genes between normal cervix and cervical cancer, including a report which analyzed 39 HOX gene expression profiles. 16 Unfortunately, there have been no studies performing such a comprehensive analysis of the different expression of HOX genes between normal ovary and ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

“…[16][17][18][19] As for the cervical cancers, several studies have shown a different pattern of expression of specific HOX genes between normal cervix and cervical cancer, including a report which analyzed 39 HOX gene expression profiles. 16 Unfortunately, there have been no studies performing such a comprehensive analysis of the different expression of HOX genes between normal ovary and ovarian cancer. In the current study, we created expression profile of 36 HOX genes using ovarian-derived samples and determined which genes were over-expressed in ovarian cancer cell lines or tissues as compared to normal ovarian tissue.…”

Section: Introductionmentioning

confidence: 99%

“…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. Another study performed by Hung et al 16 showed the results of RT-PCR analysis of 39 HOX genes in 11 cervical carcinoma cell lines. According to their study, HOXA1, B2, B4, C5, C10 and D13 genes were expressed in the majority of cervical carcinoma cell lines, but not in any of the normal cervical tissue samples.…”

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confidence: 97%

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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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“…In the gynecologic field, there are several reports describing that abnormal expression of particular HOX genes seems to be involved in cervical, ovarian and endometrial neoplasms (23)(24)(25)(26) including a recent report by Zhao et al (27). In the context of embryonic development, the expression of invasive characteristics of cancer cells might be a similar phenomenon, analogous to the movement of normal embryonic cells mediated by expression of HOX genes.…”

Section: Introductionmentioning

confidence: 99%

Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells

Yamashita

Tazawa²,

Zhao³

et al. 2006

Int J Oncol

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Abstract. HOX genes encode transcription factors that function to establish basic body pattern during embryogenesis and maintain the function of specific organs in the adult. Recent studies have demonstrated that HOX genes are also involved in oncogenesis in a range of malignancies. To elucidate whether HOX genes contribute to ovarian carcinogenesis, we created an expression profile of HOX genes using ovarian derived materials from surgical samples and epithelial ovarian cancer cells derived from five different cell lines. Real-time quantitative RT-PCR assay indicated overexpression of 14 HOX genes in clusters A and B but only 2 genes in clusters C and D. Of the 16 HOX genes, overexpression of paralogs of HOX3, HOX4 and HOX7 is seen in cluster A and B, and of HOX13 in all paralogs. In addition, HOXB7, HOXA13 and HOXB13 showed high levels of overexpression in cancer cells and tissues whereas no or little expression was observed in normal controls. To examine whether overexpressed HOX genes regulate invasion of ovarian cancer cells directly, we introduced an antisense DNA fragment of overexpressed HOXB7 and HOXB13, and HOXC5 that did not show overexpression into SKOV3 cells by electroporation. Antisense introduction followed by chemoinvasion assay using matrigel chamber demonstrated that SKOV3 cells introduced an antisense of each HOXB7 and HOXB13 showed 85% and 50% reduction of invasion ability compared to the parental SKOV3 cells, respectively. In contrast, antisense of HOXC5 introduced cells showed no significant difference of the invasion ability. These results suggest an important role of overexpressed HOX genes, especially for invasive characteristics of ovarian cancer cells.

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Homeobox gene expression and mutation in cervical carcinoma cells

Cited by 45 publications

References 27 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

Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells

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