Downregulation of TGF-ß1 suppressed proliferation and increased chemosensitivity of ovarian cancer cells by promoting BRCA1/Smad3 signaling

BACKGROUND: Studies have demonstrated that transforming growth factor beta-1 (TGF-ß1) exhibits oncogenic activity in different types of cancer, including ovarian cancer (OC). However, its regulatory mechanism in OC and whether TGF-ß1 is involved in chemosensitivity regulation remains unclear. Thus, the aim of this study was to investigate the role of TGF-ß1 in OC. METHODS: The OC cell line SKOV3 was employed, and TGF-ß1 overexpression or knockdown vectors were constructed. The cell proliferation of SKOV3 was evaluated with the cell counting kit (CCK8) kit after treatment with different concentrations of cis-platinum. Western blot and protein immunoprecipitation were employed to detect changes in BRCA1 and Smad3 expression and their interactions. Tumor growth in nude mice was evaluated. RESULTS: The results showed that TGF-ß1 knockdown increased chemosensitivity by promoting BRCA1 expression and Smad3 phosphorylation. In vivo studies showed that TGF-ß1 knockdown significantly inhibited the growth of tumors, also by upregulating BRCA1 expression and Smad3 phosphorylation. CONCLUSION: Taken together, our results suggest that TGF-ß1 knockdown inhibits tumor growth and increases chemosensitivity by promotion of BRCA1/Smad3 signaling.

Carcinoma de la mama triple negativo aspectos morfológicos y expresión de CK 5/6 / Triple negative breast cancer morphological aspects and CK 5/6 expression

El carcinoma mamario es una enfermedad heterogénea, parámetros de clasificación, factores pronósticos, no siempre predicen su curso clínico. La genética molecular, los ha estratificado en grupos diferentes a la clasificación morfológica. Trabajos respaldan que un grupo específico: carcinoma de “tipo basal” tiene peor pronóstico, es frecuentemente triple negativo, es decir: RE(-), RP(-), C-erbB-2(-) expresa citoqueratinas de epitelios basales, como la citoqueratina 5/6 (CK5/6, planteamos determinar los aspectos morfológicos de estos carcinomas, identificar la frecuencia en la que expresan CK5/6 por inmunohistoquímica, relacionarlos con parámetros clínicos disponibles. Se seleccionaron 91 carcinomas entre 2003-2008 se les realizó CK5/6. 34 (37,4 por ciento) fueron TN-CK5/6(+) y 57 (62,6 por ciento) fueron TN-CK5/6(-). Las características morfológicas descritas se observaron en ambos grupos, más frecuentemente en los carcinomas TN-CK5/6(+). La detección de estos tumores por inmunohistoquímica es una forma práctica, rentable de identificar a este grupo de peor pronóstico en la práctica diaria.

Breast cancer is heterogeneous disease classification parameters prognostic factors are not always predictors its clinical course. Molecular genetics are categorizing in different ways, as the well-known morphologic classification. Studies endorse specific group within this classifying system: Basal-like carcinomas, has worst prognosis; tends to be triple-negative: ER(-), RP(-), Erb-B2(-); expresses basal cytokeratins, such as cytokeratin 5/6 (CK5/6). Considered determining morphological aspects, frequency in which they express CK5/6 through immunohistochemistry, and contrasting them to existing clinical parameters. 91 carcinomas were selected between the years 2003-2008 and checked for CK5/6. Or the aforementioned cases, 34 (37.4 percent) resulted TN-CK5/6(+) and 57(62.6 percent) resulted TN-CK5/6(-). Morphological aspects described for and carcinomas were observed in both groups, though they were more frequent in breast carcinomas TN-CK5/6(+). For this reason, detecting these tumors using immunohistochemistry is a practical, worthwhile, and convenient way to identify this group with the worst prognosis on our daily routines.

Carcinoma medular de la mama: comportamiento clínico terapéutico / Medullar carcinoma of the breast: clinical and pathological management

Se realizó un estudio de corte transversal sobre la incidencia y manejo del cáncer medular de mama en el Instituto Autónomo Hospital Universitario de Los Andes, Estado Mérida, Venezuela. Se revisaron 624 historias clínicas de pacientes femeninas con el diagnóstico de cáncer de mama en el período comprendido de 1999 hasta 2008. Se halló una incidencia del 0,8 por ciento. La edad promedio fue 47 años. El tamaño medio fue entre 1 cm-2 cm y >2 cm-3 cm al diagnosticarlas. El 80 por ciento de las pacientes se encontraban en estadios clínicos IIA y IIB 40 por ciento cada una. Los ganglios linfáticos axilares fueron microscópicamente positivos en 80 por ciento de las pacientes. El 60 por ciento de las pacientes fueron intervenidas quirúrgicamente, el 80 por ciento se sometió a tratamiento con quimioterapia y 40 por ciento a radioterapia y quimioterapia, el 100 por ciento de las pacientes viven y las operadas no presentan recidiva tumoral.

We realized across sectional study on the incidence and management about the medullar carcinoma and to determinate its incidence and management in our media. This disease was study and performed at the Instituto Autonomo Hospital Universitario de Los Andes, Mérida state, Venezuela. We review 624 clinical charts with breast cancer from 1999 to 2008. The 0.8 percent of incidence of this disease was found. The average age was 47 years old. Average size was between 1 cm-2 cm and >2 cm-3 cm. The 80 percent of the patients were at IIA and IIB clinical stages, 40 percent each one. Axillaries lymphatic lymph nodes were microscopically positive in 80 percent of the patients, 60 percent of the patients undergone surgery, 80 percent were treated with chemotherapy and 40 percent with radiotherapy and chemotherapy. 100 percent of patients still live and the surgically treated have no tumor recurrence.

Câncer de mama triplo-negativo: aspectos clínicos, laboratoriais e terapêuticos: [revisão] / Triple negative breast cancer: clinical, loboratorial and therapeutic aspects: [review]

O câncer de mama é a neoplasia maligna mais comum entre as mulheres, e sua incidência vem aumentando de maneira consistente nas últimas décadas. A melhor compreensão anatomopatológica e molecular do câncer de mama vem permitindo observar que os diferentes subtipos desta doença apresentam características clínicas e prognósticas diferentes, além de perfil de resposta aos tratamentos diferenciados para cada subtipo. Neste artigo, serão revistos os principais aspectos clínicos, laboratoriais e terapêuticos do subgrupo de câncer de mama triplo-negativo; subgrupo de doença definido, do ponto de vista imunoistoquímico, pela ausência de receptores hormonais ou de HER-2. Esse tipo de câncer de mama representa novo desafio para os profissionais envolvidos no tratamento multidisciplinar dessa neoplasia, e vem tornando-se foco de inúmeros estudos destinados a permitir sua melhor compreensão e ao desenho de estratégias terapêuticas mais eficientes.

Breast cancer is the most common cancer among women; the incidence of such disease is increasing through the last decades. Recently, several advances regarding the understanding of the pathology and molecular biology of breast cancer directed us to a new understanding of the disease pathologic mechanisms, leading to a molecular classification and, consequently, a novel way to treat the patients. In this review we will focus on the main clinical, laboratorial and therapeutical aspects of the triple negative breast cancer, as well as on the differences and similarities among triple negative, basal-like and BRCA1 linked breast cancers.