Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Doenças Profissionais/patologia , Saúde Ocupacional/estatística & dados numéricos , Adulto , Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/genética , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/genética , Queensland/epidemiologia , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Estudos Retrospectivos , Fatores de RiscoRESUMO
MicroRNAs (miRNAs) are small non-coding RNAs of â¼20 nt in length that are capable of modulating gene expression post-transcriptionally. Although miRNAs have been implicated in cancer, including breast cancer, the regulation of miRNA transcription and the role of defects in this process in cancer is not well understood. In this study we have mapped the promoters of 93 breast cancer-associated miRNAs, and then looked for associations between DNA methylation of 15 of these promoters and miRNA expression in breast cancer cells. The miRNA promoters with clearest association between DNA methylation and expression included a previously described and a novel promoter of the Hsa-mir-200b cluster. The novel promoter of the Hsa-mir-200b cluster, denoted P2, is located â¼2 kb upstream of the 5' stemloop and maps within a CpG island. P2 has comparable promoter activity to the previously reported promoter (P1), and is able to drive the expression of miR-200b in its endogenous genomic context. DNA methylation of both P1 and P2 was inversely associated with miR-200b expression in eight out of nine breast cancer cell lines, and in vitro methylation of both promoters repressed their activity in reporter assays. In clinical samples, P1 and P2 were differentially methylated with methylation inversely associated with miR-200b expression. P1 was hypermethylated in metastatic lymph nodes compared with matched primary breast tumours whereas P2 hypermethylation was associated with loss of either oestrogen receptor or progesterone receptor. Hypomethylation of P2 was associated with gain of HER2 and androgen receptor expression. These data suggest an association between miR-200b regulation and breast cancer subtype and a potential use of DNA methylation of miRNA promoters as a component of a suite of breast cancer biomarkers.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Metilação de DNA , MicroRNAs/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Mapeamento Cromossômico , Ilhas de CpG , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Família Multigênica , Metástase Neoplásica , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Reprodutibilidade dos Testes , Sítio de Iniciação de TranscriçãoRESUMO
While oestrogen, progesterone and growth factors, including growth hormone (GH), are clearly implicated in the pathogenesis of breast cancer, there is now evidence that the newly described ghrelin axis is also involved. The aims of this study were to investigate the expression of the ghrelin axis in breast cancer tissues and cell lines and to examine the effect of ghrelin on breast cancer cell proliferation in vitro. Ghrelin and its functional receptor, the growth hormone secretagogue receptor (GHSR) type 1a, were expressed in normal breast tissue and breast cancer specimens and cell lines. In contrast, the truncated GHSR type 1b isoform was exclusively expressed in breast carcinoma, suggesting that it has potential as a diagnostic marker. Ghrelin treatment significantly increases the proliferation of the MDA-MB-435 and MDA-MB-231 breast cancer cell lines in vitro. In addition, we have described the expression of a human preproghrelin isoform, exon 3-deleted preproghrelin, which encodes mature ghrelin plus a novel C-terminal peptide. Quantitative RT-PCR was used to demonstrate that this mRNA isoform is highly expressed in the MDA-MB-435 metastatic breast cancer cell line relative to the benign MCF-10A breast epithelial cell line. The unique C-terminal peptide of exon 3-deleted preproghrelin is expressed in the glandular epithelium of breast cancer tissues, with high-grade carcinoma exhibiting the strongest immunoreactivity. The data presented here suggest that components of the ghrelin axis may represent novel markers for breast cancer and potential therapeutic targets.
Assuntos
Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Hormônios Peptídicos/metabolismo , Hormônios Peptídicos/farmacologia , Hormônios Peptídicos/fisiologia , Sequência de Aminoácidos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Grelina , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Hormônios Peptídicos/análise , Hormônios Peptídicos/genética , Isoformas de Proteínas/análise , Isoformas de Proteínas/genética , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/genética , Receptores de Grelina , Deleção de Sequência , Transcrição GênicaRESUMO
Vesicular dermatitis due to contact with Coleoptera (beetles) is common worldwide, although the condition has been infrequently described in Australia. We document the largest outbreak recognized so far in Australia with a conservative estimate of 250 cases. This occurred in central coastal Queensland over several weeks in late 1998. A survey of the medical practitioners in this district is presented, along with clinical and histopathological illustrations. Our research found that knowledge of the condition was limited even in this region where cases occur each year. This condition is an important differential diagnosis in acute blistering disorders.
