Study of the Expression of Survivin & Its Splice Variants ΔEx3, 2b and 3b as Diagnostic Molecular Markers in Breast Cancer

Survivin is a new member of the Inhibitor Apotosis Protein family (IAP) which plays an important role in the regulation of both cell cycle and apoptosis. Its distinct expression in tumor cells as compared to normal adult cells introduces Survivin as the fourth transcriptom demonstrated in tumors. Breast cancer is the most common malignancy among women and scientist`s efforts to classify it has lead to various molecular subtypes and controversial results. Because of the high prevalence of these tumors and lack of suitable molecular markers for diagnosis and prognosis, there are ongoing efforts to find molecular markers which can distinguish nontumoral from tumor tissues. In this study we evaluate the potential usefulness of Survivin and its splice variants ΔEx3, 2b and 3b as molecular markers in breast cancer. We studied 18 tumor and 17 non tumor adjacent tissues. Transcription levels were measured by Semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and normalized by ß2m as an internal control. 1)Survivin and its splice variants Δex3, 2b and 3b showed differentially higher expression levels in tumors than adjacent normal tissues. 2) The expression levels of Survivin, Survivin-ΔEx3 and Survivin-3b were significantly correlated with the type of tumors. 3) Survivin-2b was expressed in a few samples. 4) Survivin-3b was detected only in tumor samples. Also, our results showed that ΔEx3 variant can be introduced as a dominant expressed variant in breast cancer. Our data indicated that the expression of Survivin, Survivin ∆Ex3 and especially, Survivin-3b were correlated with cancerous nature of tumors and Survivin-∆Ex3 was the most common expressed variant in breast carcinomas. These results besides confirming the potential usefulness of Survivin and its splice variants as molecular markers in breast cancer, demonstrated the role of the gene and its splice variants, especially 3b in these lesions that enables distinguishing normal from tumor tissues. Therefore, evaluation of the expression of Survivin and its splice variants might be used as markers to stratify breast cancer patients for more optimal treatment modalities or it could be a promising new target for therapy.