“IDENTIFICATION AND CLASSIFICATION OF EXCLUSIVE PROTEINS FROM HER-2 POSITIVE BREAST CANCER SENSITIVE TO TREATMENT WITH TRASTUZUMAB”

Favorite this paper
How to cite this paper?
Details
  • Presentation type: IC - Undergraduate Students
  • Track: Genomics, Proteomics and Metabolomics
  • Keywords: BT474; HER2; Breast cancer; Trastuzumab; Proteomic;
  • 1 Universidade Federal do Cariri
  • 2 Universidade Federal do Estado do Rio de Janeiro
  • 3 Universidade Federal do Rio de Janeiro
  • 4 Molecular and Cell Biology Program, INCA Brazilian National Cancer Institute, RJ/Brazil.

Please log in to watch the video

Log in
Abstract

INTRODUCTION AND OBJECTIVES: Breast cancer is the most common malignancy among women worldwide. Breast cancer cells with high levels of expression of Her-2 protein are called HER2-positive. HER2-positive breast cancer - which account for 20% of breast cancer cases - tend to grow and spread faster than other types of breast cancers. Treatment with trastuzumab, a humanized monoclonal antibody targeted specifically for the extracellular domain of the Her-2 protein, was approved for the treatment of patients with HER2 positive breast cancer. This treatment brought about a significant improvement in the chance of cure for patients with this type of breast cancer, being considered one of the greatest advances in clinical oncology in recent decades. Proteomic analysis of BT474, a HER2-positive cell line sensitive to treatment with trastuzumab, can provide an overview of the mechanisms involved in these biological processes. The in-depth knowledge of the mechanisms involved in the performance of the antibody over the tumor response may allow the development of new therapies and drugs even more effective for the treatment of this pathology. In this work we investigate the differences between proteomic data obtained for BT474 cell line treated and untreated with trastuzumab. MATERIAL AND METHODS: Protein identifications were performed in a Swiss-Prot database on the MASCOT research tool (http://www.matrixscience.com/). Gene Ontology analyzes were performed on the PANTHER platform (http://pantherdb.org/). RESULTS AND CONCLUSION: Proteomic analyzes yielded a total of 897 identified proteins, 191 proteins were identified exclusively in untreated BT474 cells and 104 proteins were identified exclusively in treated BT474 cells. The classification of the Gene Ontology of these proteins exclusively identified in one of the categories showed some differences related to the treated and untreated BT474. After the effect of trastuzumab, BT474 presented exclusive proteins that participate in the biological process involved in cell adhesion and junction, in controlling the pathological states of DNA by breaking the strands and in the potent suppression of invasive activity. This preliminary proteomic study based on 1D gel comparing the BT474 cell line treated and untreated with trastuzumab suggested that more protein changes should be found with other approaches. Other proteomic investigations should be carried out to better understand the sensitivity of this type of tumor to treatment with Trastuzumab.
Keywords: BT474, HER2, Breast cancer, Trastuzumab, proteomic.
Supported by: Faperj, CNPq.

Questions (3 topics)

Share your ideas or questions with the authors!

Did you know that the greatest stimulus in scientific and cultural development is curiosity? Leave your questions or suggestions to the author!

Sign in to interact

Have a question or suggestion? Share your feedback with the authors!

Author

Raul Pinheiro

1 - Esse projeto de pesquisa já estava em desenvolvimento quando iniciei minha participação há cerca de 3 meses, assim, tive em mãos dados proteômicos e meu trabalho foi analisá-los até o presente momento.

2 - A escolha da linhagem BT474 se deu, além da presença de HER-2, por ser sensível ao tratamento com transtuzumab. Existe na literatura a presença de PTEN mutado.

3 - As modulações das vias de adesão celular foram vistas como positivas, pois a falta dessas vias favorecem o desenvolvimento de metástases. Após o tratamento com transtuzumab, de acordo com o ensaio, essa linhagem celular passou a expressar essas vias que foram identificadas apenas em células tratadas, em células não tratatadas não foi possível a identificação. 

Sim, os estudos avançarão e não ficará apenas na adesão celular, pois existem outras vias, assim como a da adesão celular, que passaram a ser identificadas após o tratamento com transtuzumab, como vias que regulam estados patológicos do DNA e vias de supressão tumoral. Esse trabalho é parte de um projeto maior que é a diferença entre a análise proteômica de células sensíveis e células resistentes ao tratamento com transtuzumab.  

Fernanda Costas Casal de Faria

Muito obrigada! E parabéns mais uma vez!

Author

Raul Pinheiro

Entender os mecanismos que fizeram aparecer essas vias e tentar explorá-los com o intuito de otimizar essa regulação.

Gilson Costa dos Santos Jr

ok

Author

Raul Pinheiro

Sim, a linhagem BT474 é HER-2 positiva. Naturalmente há um equilíbrio na expressão do receptor nas linhagens mamárias, no entanto, em 20-30% dos cânceres de mama ocorre a amplificação da expressão do HER-2.