The transcription factor c-Myc is implicated in the pathogenesis of many cancers. Among the multiple functions of c-Myc, activation of hTert and other genes involved in cellular life span contributes to its role as an oncogene. However, the ability of c-Myc to directly immortalize human cells remains controversial. We show here that overexpression of c-Myc reproducibly immortalizes freshly isolated human foreskin fibroblasts. c-Myc-immortalized cells displayed no gross karyotypic abnormalities but consisted of an oligoclonal population, suggesting that additional events cooperated to achieve immortalization. Levels of p53 and p16 were increased, but both p53-dependent DNA damage response and growth arrest in response to p16 overexpression remained intact. A marked decrease in expression of the tumor suppressor ARF occurred in several independently established c-Myc-immortalized cell lines. Methylation-specific PCR showed that the ARF gene was methylated in immortalized but not early-passage c-Myc cells, whereas p16 was unmethylated in both cell populations. Restoration of ARF expression by treatment with a demethylating agent or overexpression by a retroviral vector coincided with inhibition of proliferation and senescence of c-Myc-immortalized cells. Our findings predict that epigenetic events play a significant role in human tumors that express high levels of c-Myc.

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-06-0372DOI Listing

Publication Analysis

Top Keywords

arf expression
8
c-myc-immortalized cells
8
c-myc
7
epigenetic down-regulation
4
arf
4
down-regulation arf
4
expression selection
4
selection step
4
step immortalization
4
human
4

Similar Publications

Background: Root rot is a major disease affecting alfalfa (Medicago sativa L.), causing significant yield losses and economic damage. The primary pathogens include Fusarium spp.

View Article and Find Full Text PDF

Luffa cylindrica (L.), is a medicinal plant aimed to investigate the efficacy of the alkaloid-rich fraction (ARF) extracted from L. cylindrica.

View Article and Find Full Text PDF

The tubers of Curcuma kwangsiensis are regarded as an important medicinal material in China. In C. kwangsiensis cultivation, tuber expansion is key to yield and quality, but the regulatory mechanisms are not well understood.

View Article and Find Full Text PDF

Background: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B-cell-specific Moloney murine leukemia virus insertion site-1 (Bmi-1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation.

View Article and Find Full Text PDF

A Novel Hollow Core Antiresonant Fiber-Based Biosensor for Blood Component Detection in the THz Regime.

Biomed Phys Eng Express

January 2025

Electronics and Communication Engineering, SRM Institute of Science and Technology (Deemed to be University), Tech Park, SRM Nagar, Kattankulathur, Kattankulathur, Tamilnadu, 603203, INDIA.

This article proposes a novel biosensor based on a five-semi-circular cladding tube hollow core antiresonant fiber (HC-ARF) with a frequency range of 0.5-2.8 THz, using Zeonex as the background material.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!