Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas

Cantile, Monica; Cindolo, Luca; Napodano, G.; Altieri, Vincenzo; Cillo, Clemente

doi:10.1038/sj.onc.1206808

Cited by 64 publications

(61 citation statements)

References 51 publications

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“…[21][22][23] Therefore, the microenvironment including such hormones and growth factors may promote metastasis via changes of some HOX gene expressions. As HOXC4 is one of the HOX genes that are active in most of the human bladder cancer and malignant prostate cancer, 11,24 the HOXC4 overexpression may be one of the common pathways by which cancer cells are converted into more malignant phenotypes in these cancers, including melanoma. It is of interest that the expression of HOXB13 increased in melanoma with distant metastasis because the expressions of other HOX genes belonging to paralogy 13 (HOXA13, C13 and D13) were also different between melanoma and nevus.…”

Section: Discussionmentioning

confidence: 99%

“…10 Increased expressions of HOXC4, C5, C6 and C11 are likely to be involved in the development of human bladder transitional cell carcinomas. 11 Experimental biologic approaches showed that misexpression of some HOX genes converted tumor cells into more malignant ones. Forced expression of HOXA1 in human breast cancer cells resulted in increased cell growth activity.…”

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confidence: 99%

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Altered expressions of HOX genes in human cutaneous malignant melanoma

Maeda

Hamada

Takahashi

et al. 2004

Intl Journal of Cancer

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HOX genes act as master genes to control morphogenesis. In human, HOX genes form 4 clusters composing 9 to 11 HOX genes (39 genes in total) on different chromosomes. We hypothesized that aberrant expression of HOX genes was associated with development and subsequent progression of melanoma and that the 39 HOX gene expression pattern determined the sites where melanoma grew. The expression levels of 39 HOX genes in 15 human cutaneous melanoma specimens and 7 nevus pigmentosus specimens were quantified by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA11, A13, B9, D12 and D13 in melanoma were higher than those in nevus pigmentosus and that the expression levels of HOXA11, B2 and C13 were significantly different between pT4 melanoma and pT1 to pT3 melanoma. It was most notable that the expression levels of HOXA1, A2, C4 and B13 in melanoma with distant metastasis were higher than those in melanoma without it. On the other hand, we found no relationship between HOX genes expression patterns and the growing sites of melanoma. These results indicated that the misexpressions of some specific HOX genes were implicated in melanoma genesis and metastasis but had no linkage with melanoma sites. © 2004 Wiley-Liss, Inc. Key words: melanoma; HOX; metastasis; nevus pigmentosusHox genes are one of the master regulators of morphogenesis and cell differentiation during embryogenesis of animals. 1 The genes contain a 180 bp DNA sequence (homeobox), which encodes a highly conserved 60 amino acid homeodomain. The HOX proteins function as transcription factors through their homeodomain, which is responsible for recognition and binding of sequence-specific DNA motifs. 2,3 In human genome, 39 HOX genes are clustered in a similar arrangement of 13 paralog groups in 4 different chromosomal regions, HOXA, B, C and D. 4 During embryonic morphogenesis, the HOX genes determine positional identity along the anterior-posterior and secondary axes in animals. Within each cluster, HOX genes located at the 3Ј extremity are activated first and in anterior embryonic domains, whereas 5Ј-located genes are transcribed subsequently and in more caudal areas, which is the property called colinearity rule. 5 HOX genes are also expressed in some normal adult organs in characteristic patterns, suggesting their possible role in the maintenance of tissuespecific architecture besides their roles in embryogenesis. 6 -9 Comparative analysis of HOX gene expression between cancerous tissues and normal tissues uncovered the dysregulated expression(s) of a particular HOX gene(s) in some kinds of carcinomas. For example, HOXB5 and B9 are expressed in normal kidney but not in renal cancer, whereas the expression of HOXC11 is observed in human renal cancer but not in normal kidney. 6 In human prostate cancer, overexpression of HOXC8 correlates with loss of differentiated phenotype. 10 Increased expressions of HOXC4, C5, C6 and C11 are likely to be involved in the development of human bladder transitiona...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Altered expressions of HOX genes in human cutaneous malignant melanoma

Maeda

Hamada

Takahashi

et al. 2004

Intl Journal of Cancer

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“…Dysregulated HOX gene expressions were found in various human cancers, such as lung cancer,2 bladder cancer 3…”

Section: Introductionmentioning

confidence: 99%

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

Zhou

Xie

et al. 2018

Cancer Medicine

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The cancers are the leading cause of disease‐related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11‐AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11‐AS in different human malignancies. The expression of HOXA11‐AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11‐AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11‐AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11‐AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11‐AS‐targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.

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“…Some HOX genes exhibit different expression levels in a variety of human cancers including kidney, colon, bladder, melanoma and prostate cancers, compared to normal tissues from which they were derived (6)(7)(8)(9)(10). For example, HOXB5 and B9 are expressed in normal kidney but not in renal cancer whereas the expression of HOXC11 is observed in human renal cancer but not in normal kidney (6).…”

Section: Introductionmentioning

confidence: 99%

Disordered expression of HOX genes in human non-small cell lung cancer

Abe

Hamada²,

Takahashi³

et al. 2006

Oncol Rep

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We hypothesized that the disordered tissue architecture in cancer results from the steps that the cells execute the program designed during ontogeny in a spatiotemporally inappropriate manner. HOX genes are known as master regulators of embryonic morphogenesis, and encode transcription factors which regulate the transcription of the downstream genes to realize the program of body plan. In this study, we quantified the expression levels of 39 HOX genes in 41 human non-small cell lung cancer (non-SCLC) and non-cancerous lung tissues by a comprehensive analysis system based on the realtime RT-PCR method. We found that the expression levels of HOXA1, A5, A10 and C6 in squamous cell carcinoma tissues (and HOXA5 and A10 in adenocarcinoma tissues) were significantly higher than those in the non-cancerous tissues. Comparison of HOX gene expressions between adenocarcinoma and squamous cell carcinoma tissues showed higher expressions of HOXA1, D9, D10 and D11 in squamous cell carcinoma tissues than in adenocarcinoma tissues. Immunohistochemical analysis revealed that HOXA5 and A10 proteins were localized in the cytoplasm of tumor cells in both adenocarcinoma and squamous cell carcinoma tissues. These results suggest that the disordered patterns of HOX gene expressions were involved in not only the development of non-SCLC but also histological diversity such as adenocarcinoma and 4 squamous cell carcinoma.

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Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas

Cited by 64 publications

References 51 publications

Altered expressions of HOX genes in human cutaneous malignant melanoma

Altered expressions of HOX genes in human cutaneous malignant melanoma

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

Disordered expression of HOX genes in human non-small cell lung cancer

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