RESUMO
BACKGROUND: Upregulation of estrogen receptor beta (ERß) in breast cancer cells is associated with epithelial maintenance, decreased proliferation and invasion, and a reduction in the expression of the receptor has been observed in invasive breast tumors. However, proof of an association between loss of ERß and breast carcinogenesis is still missing. METHODS: To study the role of ERß in breast oncogenesis, we generated mouse conditional mutants with specific inactivation of ERß and p53 in the mammary gland epithelium. For epithelium-specific knockout of ERß and p53, ERß F/F and p53 F/F mice were crossed to transgenic mice that express the Cre recombinase under the control of the human keratin 14 promoter. RESULTS: Somatic loss of ERß significantly accelerated formation of p53-deficient mammary tumors. Loss of the receptor also resulted in the development of less differentiated carcinomas with stronger spindle cell morphology and decreased expression of luminal epithelial markers. CONCLUSIONS: Our results show that synergism between ERß and p53 inactivation functions to determine important aspects of breast oncogenesis and cancer progression.
Assuntos
Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Receptor beta de Estrogênio/genética , Proteína Supressora de Tumor p53/genética , Alelos , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transição Epitelial-Mesenquimal/genética , Epitélio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Expressão Gênica , Inativação Gênica , Genótipo , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Camundongos , Camundongos Transgênicos , Fenótipo , Prognóstico , Proteína Supressora de Tumor p53/metabolismoRESUMO
RESUMEN Introducción: la vacuna contra el virus del papiloma humano es la medida preventiva más reciente y controversial para el cáncer de cuello uterino. En 2014 Colombia tuvo una serie de supuestas reacciones adversas ante la vacuna que provocó la caída de su cobertura. Objetivo: describir los conocimientos frente al virus del papiloma humano y su vacuna en los padres de Rivera, Huila. Materiales y método: estudio transversal con muestra por conveniencia de 124 padres de niños menores de 18 años, a través de una encuesta sociodemográfica donde fue medido el conocimiento acerca del virus, su vacuna y el cáncer de cérvix. Análisis cuantitativo por medio de la técnica de frecuencias simples. Resultados: el nivel de conocimiento fue bajo (44,35%); el 43,54% identifican al virus del papiloma humano como agente etiológico del cáncer de cuello uterino; sólo el 7,4% considera útil la vacuna como método preventivo y la vacuna fue aceptada por el 87% de los padres. Conclusiones: El conocimiento del virus del papiloma humano y el cáncer de cuello uterino es bajo y se ve afectado por el desconocimiento de las diferentes estrategias preventivas del cáncer de cuello uterino, así como por la falta de información sobre la acción de la vacuna contra el virus. Sin embargo, la aceptabilidad de la vacuna es alta. MÉD.UIS. 2017;30(1):13-9.
ABSTRACT Introduction: Human Papillomavirus Vaccine is the most recent and controversial step for cervical cancer prevention. During 2014, in Colombia, a series of suspected adverse reactions to the vaccine caused a decline in its coverage. Objective: the aim of this study is to describe the knowledge about Human Papillomavirus and its vaccine from parents of Rivera, Huila. Materials and method: cross-sectional study with a convenient sample of 124 parents whose children were under 18 years old; through a socio-demographic questionnaire, knowledge about issues related to the virus, related to cervical cancer and its vaccine was measured. A quantitative analysis was performed by simple frequency analysis. Results: the level of knowlodge was low (44,35%); 43,54% of the parents identify Human Papillomavirus as an etiological cervical cancer agent, just 7,4% of the parents consider the vaccine as an useful preventive method and the vaccine was accepted by 87% of the parents. Conclusions: the knowledge level of the parents of Rivera, Huila about Human Papillomavirus and cervical cancer is low and it is affected by the ignorance of the different cervical cancer preventive strategies, as well as the lack of information of the action of Human Papillomavirus vaccine. However, the vaccine acceptability is high. MÉD.UIS. 2017;30(1):13-9.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Pais , Aceitação pelo Paciente de Cuidados de Saúde , Neoplasias do Colo do Útero , Colômbia , Conhecimento , Infecções por Papillomavirus , GinecologiaRESUMO
In 1998, an estrogen receptor ß (ERß) knockout (KO) mouse was created by interrupting the gene at the DNA binding domain (DBD) with a neocassette. The mutant females were subfertile and there were abnormalities in the brain, prostate, lung, colon, and immune system. In 2008, another ERß mutant mouse was generated by deleting ERß exon 3 which encodes the first zinc finger in the DBD. The female mice of this strain were unable to ovulate but were otherwise normal. The differences in the phenotypes of the two KO strains, have led to questions about the physiological function of ERß. In the present study, we created an ERß exon 3-deleted mouse (ERß-Δex3) and confirmed that the only observable defect was anovulation. Despite the two in-frame stop codons introduced by splicing between exons 2 and 4, an ERß protein was expressed in nuclei of prostate epithelial cells. Using two different anti-ERß antibodies, we showed that an in-frame ligand binding domain and C terminus were present in the ERß-Δex3 protein. Moreover, with nuclear extracts from ERß-Δex3 prostates, there was an ERß-dependent retardation of migration of activator protein-1 response elements in EMSA. Unlike the original knockout mouse, expression of Ki67, androgen receptor, and Dachshund-1 in prostate epithelium was not altered in the ERß-Δex3 mouse. We conclude that very little of ERß transcriptional activity depends on binding to classical estrogen response elements (EREs).
Assuntos
Receptor beta de Estrogênio/genética , Éxons/genética , Elementos de Resposta/genética , Deleção de Sequência/genética , Transdução de Sinais/genética , Animais , DNA/metabolismo , Feminino , Regulação da Expressão Gênica , Marcação de Genes , Masculino , Camundongos Mutantes , Ovário/fisiopatologia , Próstata/metabolismo , Próstata/patologia , Ligação Proteica/genética , Transporte Proteico , Receptores Androgênicos/metabolismo , Reprodutibilidade dos Testes , Fator de Transcrição AP-1/metabolismoRESUMO
Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the 'normal' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that Cyr61 is sufficient to induce MCF-7 cells to grow in the absence of E2. Cyr61-transfected MCF-7 cells (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7 cells transfected with the vector DNA (MCF-7/V) remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ER alpha expression in MCF-7/Cyr61 cells is decreased although still functional. Moreover, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and antiestrogen-resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.
Assuntos
Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Estradiol/análogos & derivados , Estrogênios , Proteínas Imediatamente Precoces/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas de Neoplasias/fisiologia , Neoplasias Hormônio-Dependentes/patologia , Adenocarcinoma/metabolismo , Neoplasias da Mama/metabolismo , Colágeno , Proteína Rica em Cisteína 61 , Progressão da Doença , Regulação para Baixo , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Fatores de Crescimento Endotelial/biossíntese , Estradiol/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Receptor alfa de Estrogênio , Feminino , Fulvestranto , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Imediatamente Precoces/genética , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/genética , Laminina , Linfocinas/biossíntese , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Neoplasias Hormônio-Dependentes/metabolismo , Proteoglicanas , Receptores de Estrogênio/biossíntese , Receptores de Estrogênio/genética , Proteínas Recombinantes de Fusão/fisiologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/patologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
El presente trabajo es un estudio descriptivo de corte transversal, realizado en los estudiantes del II Ciclo del Programa de Profesionalización para Técnicos de Laboratorio, de la Escuela de Tecnología Médica de la Facultad de Medicina Alberto Hurtado de la Universidad Peruana Cayetano Heredia, durante los meses de febrero y marzo de 1998. Tuvo como objetivo determinar la relación de hábitos de estudio y rendimiento académico, así como identificar si el interés en obtener el Título profesional y la actividad que realiza actualmente influyen en ambas variables. La recolección de datos se realizó en forma directa a través de dos instrumentos: el primero un cuestionario, para la obtención de datos personales; el segundo fue el inventario de Hábitos de estudio de Wilbert Wrenn. La población de estudio estuvo constituída por 257 estudiantes, los cuales fueron sometidos a criterios de inclusión y exclusión, obteniéndose de ellos una muestra de 139 estudiantes, cuyas edades fluctuaban entre 21 y 30 años, cabe resaltar que el número de mujeres supera al de varones en una proporción de 2 a 1, siendo la mayoría solteros, que estudian y trabajan actualmente. Para evaluar el rendimiento académico de los estudiantes se consideraron las notas del I ciclo, proporcionadas según Código del Alumno por la Secretaría Académica de la Escuela de Tecnología Médica, asegurándose así la confidencialidad de la información. Para el análisis estadístico se utilizó la prueba de chi cuadrado y el analísis de correlación de Pearson. Se encontró relación significativa entre hábitos de estudio y la nota final obtenida en cada uno de los cursos que conforman el promedio general. Así mismo los resultados obtenidos demuestran que, el interés por obtener el Título Profesional y la actividad que realizan actualmente se relaciona con el rendimiento académico, expresado como promedio general.
