No abstract

Identification of cancer-associated genes is critical for developing effective treatments of colorectal cancer (CRC). A limited number of studies have examined the mechanisms and genes underlying CRC. Abnormal transforming growth factor beta (TGF-β) expression was observed at different stages of carcinoma. We examined the effect of cancer-related cytokine TGF-β on carbonic anhydrase (CA) III gene expression in colon cancer HT-29 cells. TGF-β (500 U/mL) downregulated CAIII gene expression at both the mRNA and protein levels. Transient transfection experiments indicated that different CAIII promoter constructs were active in HT-29 cells. TGF-β reduced transcriptional activity of all promoter constructs, indicating that the potential response element for TGF-β-directed transcription lies within the-108/+86 region of the CAIII promoter. According to the non-Smad pathway inhibitory assay, TGF-β downregulated the CAIII gene through mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phosphoinositide-3-kinase (PI3K) pathways. The same decreasing effect was determined in the Saos-2, osteosarcoma cell line, indicating that the effect of TGF-β on CAIII was not tissue-specific. However, examination of PI3K and MAPK/ERK signaling pathways with suitable inhibitors revealed that the PI3K but not the MAPK/ERK pathway was responsible for TGF-β downregulation.

Karbonik anhidraz enzim ailesinin üyeleri karbondioksitin bikarbonat iyonuna geri dönüşümlü hidratasyonunu katalizleyerek dokulardaki CO2 taşınımını, pH dengesini, solunum reaksiyonlarını, iyon dengesini, biyolojik reaksiyonları ve kemik oluşumu gibi birçok önemli süreci katalizleyen ailenin kasa spesifik üyesi olan Karbonik Anhidraz III (CAIII)’ün kolon kanser modeli HT-29 hücre hattında EGF etkili mRNA düzeyindeki ekspresyon seviyesi analiz edilmiştir. Özellikle hücrenin hayatta kalması, büyümesi, invazyonu ve proliferasyonu gibi önemli mekanizmaları regüle eden EGF sitokininin CAIII mRNA seviyesini düşürdüğü bu çalışma ile belirlenmiştir.

Apoptosis, called programmed cell death, is one of the most important cellular mechanisms regulating the elimination of harmful and unnecessary cells. This tightly regulated suicide program is very important in the development and maintenance of tissue homeostasis. Disruption of apoptosis, also called natural defense mechanism, causes abnormal cellular proliferation and the emergence of genetic defects. Disruption of the apoptotic mechanism often results in tumorigenesis. Apoptosis can be induced by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as binding of ligands to death receptors on the cell surface. Apoptotic signaling pathways are regulated by many proteins, including BCL-2 family proteins, apoptosis inhibitor (IAP) proteins, and FLICE-inhibitor protein. This book chapter includes a review of the signaling pathways associated with apoptosis.