HTLV-I Tax-Mediated Inactivation of Cell Cycle Checkpoints and DNA Repair Pathways Contribute to Cellular Transformation: “A Random Mutagenesis Model”
Journal Title: Journal of Cancer Sciences - Year 2015, Vol 2, Issue 2
Abstract
To achieve cellular transformation, most oncogenic retroviruses use transduction by proto-oncogene capture or insertional mutagenesis, whereby provirus integration disrupts expression of tumor suppressors or proto-oncogenes. In contrast, the Human T-cell leukemia virus type 1 (HTLV-I) has been classified in a separate class referred to as “transactivating retroviruses”. Current views suggest that the viral encoded Tax protein transactivates expression of cellular genes leading to deregulated growth and transformation. However, if Tax-mediated transactivation was indeed sufficient for cellular transformation, a fairly high frequency of infected cells would eventually become transformed. In contrast, the frequency of transformation by HTLV-I is very low, likely less than 5%. This review will discuss the current understanding and recent discoveries highlighting critical functions of Tax in cellular transformation. HTLV-I Tax carries out essential functions in order to override cell cycle checkpoints and deregulate cellular division. In addition, Tax expression is associated with increased DNA damage and genome instability. Since Tax can inhibit multiple DNA repair pathways and stimulate unfaithful DNA repair or bypass checkpoints, these processes allow accumulation of genetic mutations in the host genome. Given this, a “Random Mutagenesis” transformation model seems more suitable to characterize the oncogenic activities of HTLV-I.
Authors and Affiliations
Christophe Nicot
Keywords
Related Articles
- EP ID EP209343
- DOI 10.13188/2377-9292.1000009
- Views 108
- Downloads 0
Can Ki-67 Predict Pelvic Node Status in Endometrial Adenocarcinoma?
Background: The Ki-67 marker is a nuclear protein that has a direct correlation with the degree of cells proliferation that often expressed in human neoplasm. Objective: To evaluate utilization of Ki-67 expression as pr...
White Adipose Tissue Browning and Cancer Cachexia
Cachexia or wasting syndrome is often seen in cancer patients. Over half of the patients suffer from this condition although the incidence varies from tumor types. Symptoms of cancer cachexia include progressive weight l...
The Association amongst ‘Triple Negative’ Breast Cancers, Lymph Node Metastasis, Disease Free and Overall Survival
Triple negative’ breast cancer (TNBC) has fewer specific targets for systemic therapy. We hypothesized that patients with TNBC have an increased incidence of sentinel lymph node (SLN) metastases and decreased disease-spe...
Evaluation of Prostate CancerDetection Rates in PatientsUndergoing TransrectalUltrasound (TRUS) GuidedProstate Biopsy
Background: Prostate cancer is one of the most common types of organ cancer among males in Turkey as well as all over the world. The gold standard method for histopathological diagnosis of prostate cancer is Trans rectal...
HTLV-I Tax-Mediated Inactivation of Cell Cycle Checkpoints and DNA Repair Pathways Contribute to Cellular Transformation: “A Random Mutagenesis Model”
To achieve cellular transformation, most oncogenic retroviruses use transduction by proto-oncogene capture or insertional mutagenesis, whereby provirus integration disrupts expression of tumor suppressors or proto-oncoge...