Abstract 250: Apoptosis-associated genes related to photodynamic therapy in breast carcinomas

Abstract

Breast carcinoma is a heterogeneous disease with different molecular subtypes being characterized by distinct morphological appearances, genetic alterations, and clinical presentation. This heterogeneity is the major challenge in its diagnosis and treatment. Photodynamic therapy (PDT) has been used as an alternative treatment to the conventional therapies, and it is becoming accepted as a therapeutic modality in oncology. PDT is based on the incorporation of photosensitizing molecules into tumors and, after excitation with light, induces direct tumor cell death as well as indirect effects on the tumor microenvironment. Cellular apoptosis is the main event found in all tumor tissues treated by PDT. To date, metabolic pathways influenced by PDT have not been fully elucidated, and studies involving gene expression analysis in mammary tumors after PDT are scarce. Therefore, the aim of this study was to find molecular markers involved in the apoptosis pathways that may be related to the effect of PDT in breast carcinomas. To this end, global gene expression profiles were obtained from primary breast tumors samples induced in 20 female rats Sprague-Dawley, being 10 from untreated tumor samples (group 1 or control group) and 10 breast tumors samples submitted to PDT (group 2 or treatment group). These samples were investigated by quantitative real time PCR (qRT-PCR) using the Rat Apoptosis RT2 Profiler™ PCR Array platform (Super-Array, USA) that consists of 84 genes of interest involved in the modulation of cellular apoptosis. A set of 11 genes presented different expression when comparing the groups. The HRK, BIK, CASP14, CIDEA, GADD45a, TNF, CASP1 genes showed up regulation significance at treatment group compared with the control group (Student's t-test, P<0,05). These genes play a role of induction of apoptosis among other functions. TNF-tumor necrosis factor gene, for example, plays a role in the regulation of cell proliferation, induction of apoptosis, and inflammatory response. The GADD45a may mediate a delay in G2 to M cell cycle progression, which could induce DNA repair. The BIRC5, CASP6, TNFRSF11b, TP53 genes showed down expression significance in the treatment group compared with the control (Student's t-test, P<0,05). BIRC5 gene act as an inhibitor of programmed cell death preventing or reducing the activity of caspases in any cysteine proteases groups involved in the apoptosis. These results showed that these apoptosis-associated genes could explain the rapid elimination of tumor that occurs after PDT applications in breast carcinomas, and may thus contribute to better understanding of both the breast carcinogenesis and the PDT action mechanism. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 250. doi:1538-7445.AM2012-250