Expression pattern of the class I homeobox genes in ovarian carcinoma

Lee, Jae Kwan; Park, Joong Jean; Lee, Nak Woo; Lee, Kyu Wan; Na, Jung Yeol

doi:10.3802/jgo.2010.21.1.29

Cited by 20 publications

(17 citation statements)

References 32 publications

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“…Slightly different results were found in a more recent study by Hong et al (2010) [16]. In this study the expression of 36 HOX genes in ovarian cancer cell lines and tissues were compared to normal ovarian tissue, revealing a difference in expression of 11 HOX genes ( HOXA7 , B3 , B4 , B6 , C10 , C11 , D1 , D3 , D10 , D11 and D13 ).…”

Section: Introductioncontrasting

confidence: 58%

HOX genes in ovarian cancer

et al. 2011

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The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

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Section: Introductioncontrasting

confidence: 58%

HOX genes in ovarian cancer

et al. 2011

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“…We found that 9 out of the 10 HOXB genes were upregulated, the most significant being HOXB4 , B5 , B7 and B13 . HOXB4 upregulation has been shown to be associated with the development of platinum resistance in cell lines, and its over‐expression in ovarian cancer has been reported previously in a relatively small study using only 4 cell lines and 7 ovarian cancer tumour samples, but no oncogenic function for this gene has been proven. HOXB4 has been implicated as a cancer‐related gene in other malignancies, including breast cancer, leukaemia and lung canceR .…”

Section: Discussionmentioning

confidence: 86%

The prognostic significance of specific HOX gene expression patterns in ovarian cancer

Kelly

Möller-Levet

McGrath

et al. 2016

Intl Journal of Cancer

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HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.Ovarian cancer is the 5th leading cause of cancer death in women in the western world and it is estimated there were 22,280 new cases and 15,500 deaths due to the disease in the US in 2012. 1 It is the most lethal of the gynaecological malignancies largely due to late diagnosis. Standard treatment involves debulking surgery followed by a combination of taxane and platinum-based therapy. Initially most women respond to platinum-based therapy, but the majority suffer disease recurrence due to drug resistance. It is therefore essential to introduce new therapeutic approaches to improve treatment at diagnosis and/or provide an effective second line treatment.There are different types of ovarian cancer classified by the cell type they originate from. The most common form, accounting for >90% of ovarian cancers, is epithelial ovarian cancer (EOC), and the high grade serous (HGS) subtype accounts for 80% of EOC cases.The epithelial ovarian tumours undergo M€ ullerian differentiation, which suggests that differentiation-regulatory factors may contribute to their progression. This mechanism has been shown to involve homeobox (HOX) genes 2,3 which play important roles in tissue differentiation during embryonic development. The HOX genes constitute a family of transcription factors, and in mammals 39 HOX genes have been identified. They are organised into 4 paralogous clusters (A, B, C and D) located on 4 different chromosomes. During development of the female reproductive system four HOX genes, HOXA9, HOXA10, HOXA11 and HOXA13 are expressed uniformly along the M€ uller...

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“…These cell lines were maintained in minimal essential medium (Life Technologies, Inc, Grand Island, NY) supplemented with 10% fetal bovine serum and 100 Kg/mL of streptomycin. Cell lines were maintained in a humidified 5% CO 2 incubator at 37-C. 20 Establishment of Paclitaxel-Resistant EOC Cells SKOV3 cells were washed thoroughly with phosphatebuffered saline (PBS) and then transferred to RPMI-1640 medium containing 10% fetal bovine serum and 100 Kg/mL of streptomycin. The cells were continuously exposed to increasing doses of paclitaxel for more than 6 months, during which time the medium was replaced every 3 days.…”

Section: Ovarian Cancer Cell Lines and Culturementioning

confidence: 99%