Oncohematology and Genetics

Endocrine Tumorigenesis and Hormonal Regulation of cancer


Cód. SSPA: IBiS-C-08

The role of PTTG1 securin in the development and progression of different neoplasias, as well as its possible application as a tumour marker.

Protein PTTG1 is homologous to Xenopus securin and is expressed abundantly in a wide range of tumours of different tissue origin. Human securin, hPTTG, takes part in the control of chromatid separation, and its anomalous expression promotes a deregulated segregation of chromosomes and the appearance of aneuploidies. The overexpression of PTTG1 could have relevance as a tumour marker as it is associated with tumours exhibiting a high degree of malignancy and the appearance of metastasis. We study the relationship between the overexpression of PTTG1 and chromosomal instability and its role in pre-invasive cancerous lesions. We also examine the role of PTTG1 securin in the modulation of tumour cell sensitivity to chemotherapeutic agents which affect the stability of microtubules. Finally, we study the capacity for tumour cell invasion in relation to PTTG1 expression levels and the expression of proteins related to invasion and metastasis, which are induced by PTTG1. These lines of work are undertaken in collaboration with groups from the University of Seville and CSIC.

Mechanisms of blocking apoptosis pathways responsible for progression and hormone resistance in hormone-dependent cancer.

Prostate cancer is one of the world's main causes of death by cancer. A high proportion of prostate cancers are diagnosed in advanced stages, in which androgenic deprivation is a palliative treatment that improves survival outcomes. Most patients evolve to a state of hormone independence, although the mechanisms underlying this phenomenon remain unclear. Defects in apoptosis signalling pathways are frequent in tumour cells and the imbalance these alterations produce to thereby increase cell survival plays an important role in both tumour progression and in the response to chemotherapy. Proteins of the Bcl-2 family play a critical role in the activation of the mitochondrial apoptotic route. Neoplastic cells develop specific mechanisms to avoid apoptosis which are involved in tumour progression and the development of resistance to different therapeutic agents. Our working hypothesis is based on the possible mechanisms that block the pro-apoptotic proteins Bax and Bak, in which anti-apoptotic members of the Bcl-2 family take part, especially Bcl-xL, as well as other proteins such as Ku70 and PTTG1. We study the presence of these interactions in non-stimulated cells as well as in cells treated with different stimuli to determine the possible involvement of these interactions in the resistance to apoptosis.

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