Kimyasal Olarak Etkilenen Deri Karsinojenisinin Fare Modelinde SATB1 ve SATB2 Ekspresyonunun Analizi

Abstract

AT açısından zengin özel sekans bağlayıcı proteinler (SATB) 1 ve yakından ilişkili SATB2'nin, genomik DNA'ya kromatin yeniden modelleme/modifiye enzimleri ve transkripsiyon faktörlerini görevlendirerek kromatin yapısını ve gen ekspresyonunu düzenleyen genom düzenleyicileri olarak görev yaptığı öne sürülmüştür. SATB1 ve SATB2 ekspresyon seviyelerindeki değişikliklerin lenfoma, kolorektal ve meme kanseri hücreleri gibi çeşitli kanser hücrelerinde tümör büyümesi ve metastaz gelişimi ile ilişkili olduğu gösterilse de SATB1 ve SATB2 gen aktivitesinin tümörlerdeki potansiyel rolü Cildin durumu için hala bilinmiyor. Bu çalışmada, kimyasal olarak indüklenen karsinojenezin erken ve orta aşamalarında fare derisinde SATB1 ve SATB2 ekspresyon seviyeleri kantitatif RT-PCR analizi ile araştırıldı. Burada hem SATB1 hem de SATB2'nin cilt karsinogenezinin orta aşaması (papillomlar) sırasında aşağı regüle edildiği bulundu. Ayrıca SATB1'in SATB2'ye göreli ekspresyon seviyelerinin karşılaştırılması, SATB2'nin cilt karsinojenezinin orta aşamasında daha büyük bir aşağı regülasyona sahip olduğunu göstermiştir. Bu veriler, göreceli gen ekspresyon seviyelerini belirleyip karşılaştırarak SATB1 ve SATB2'nin cilt karsinogeneziyle ilişkisi hakkında temel bir bilgi ve öngörü sağlar.

Keywords

• SATB1
• SATB2
• cilt karsinogenezi

Analysis of SATB1 and SATB2 Expression in the Mouse Model of Chemically Induced Skin Carcinogenesis

Abstract

Special AT-rich sequence binding proteins (SATB) 1 and the closely related SATB2 have been proposed to act as genome organizers that regulate chromatin structure and gene expression by recruiting chromatin remodelling/modifying enzymes and transcription factors to genomic DNA. Despite the fact that the changes in the expression levels of SATB1 and SATB2 were shown to be associated with tumour growth and metastasis development in various cancer cells such as lymphoma, colorectal and breast cancer cells, the potential role of SATB1 and SATB2 gene activity in tumours of the skin is still unknown. In the present study, SATB1 and SATB2 expression levels were investigated in mouse skin at early and middle stages of chemically induced carcinogenesis by quantitative RT-PCR analysis. Here, it was found that both SATB1 and SATB2 were down-regulated during the middle stage (papillomas) of skin carcinogenesis. Furthermore, the comparison of the relative expression levels of SATB1 to SATB2 has shown that SATB2 has a greater down-regulation in the middle stage of skin carcinogenesis. These data provide a fundamental knowledge and insight about SATB1 and SATB2 association with the skin carcinogenesis by determining and comparing their relative gene expression levels.

Keywords

• SATB1
• SATB2
• skin carcinogenesis

Supporting Institution

Cyprus International University and University of Bradford

Ethical Statement

All animal works were performed under the license of the University of Bradford (Bradford, UK) and the Institutional Animal Care and Use Committee protocol of Boston University (Boston, MA, USA). This research was conducted in accordance with the ethical standards set forth by University of Bradford and Cyprus International University, and complies with the ethical guidelines and principles for scientific research.

Thanks

I would like to thank Dr. Michael Fessing, Dr. Natalia V. Botchkareva, and Dr. Andrei Mardaryev for their supports, technical advises and encouragements. I also thank to the members of the G and M floor Laboratories for their helpful assistance and discussions. This work was supported by The University of Bradford and The Cyprus İnternational University.

References

1. Ghazizadeh, S., and L.B. Taichman, Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. EMBO J, 2001. 20: p. 1215-1222. DOI: 10.1093/emboj/20.5.1215
2. Hall, P.A., and F.M. Watt, Stem cells: the generation and maintenance of cellular diversity. Development, 1989. 106: p. 619-633. DOI: 10.1242/dev.106.4.619
3. Lavker, R.M., S. Miller, C. Wilson, G. Cotsarelis, Z.G. Wei, J.S. Yang, and T.T. Sun, Hair follicle stem cells: their location, role in hair cycle, and involvement in skin tumor formation. J Invest Dermatol, 1993. 101: p. 16S-26S. DOI: 10.1111/1523-1747.ep12327004
4. Berenblum, I., N. Haran-Ghera, and N. Trainin, An experimental analysis of the hair cycle effect in mouse skin carcinogenesis. Br J Cancer, 1958. 12: p. 402-413. DOI: 10.1038/bjc.1958.52
5. Blanpain, C., and E. Fuchs, Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol, 2009. 10: p. 207-217. DOI: 10.1038/nrm2636
6. Blanpain, C., and E. Fuchs, Epidermal stem cells of the skin. Annu Rev Cell Dev Biol, 2006. 22: p. 339-373. DOI: 10.1146/annurev.cellbio.22.010305.104318
7. Ambler, C.A., and A. Maatta, Epidermal stem cells: location, potential and contribution to cancer. J Pathol, 2009. 217: p. 206-216. DOI: 10.1002/path.2459
8. Alvarez, J.D., D.H. Yasui, H. Niida, T. Joh, D.Y. Loh, and T. Kohwi-Shigematsu, The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes Dev, 2000. 14: p. 521-535. DOI: 10.1101/gad.14.5.521

9. Cai, S., H.J. Han, and T. Kohwi-Shigematsu, Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat Genet, 2003. 34: p. 42-51. DOI: 10.1038/ng1133