The polycomb group (PcG) protein Bmi1 plays an essential role in the self-renewal of hematopoietic and neural stem cells. Derepression of the Ink4a/Arf gene locus has been largely attributed to Bmi1-deficient phenotypes in the nervous system. However, its role in hematopoietic stem cell (HSC) self-renewal remained undetermined. In this study, we show that derepressed p16(Ink4a) and p19(Arf) in ...

Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation of the p16(INK4a)/pRB pathway is required in addition to telomere maintenance for the immortalization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be explained by an inadequate...

The p16(INK4A) (hereafter p16) tumor suppressor is encoded by the INK4A/ARF locus which is among the most commonly dysregulated sequences in human cancer. By inhibiting cyclin-dependent kinases, p16 activates the G1-S checkpoint, and this response is often considered to be critical for establishing a senescence-like growth arrest. Not all studies support a universal role for p16 in senescence. ...

Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. Here, we examine growth suppression effic...

Fucoidan is known to have various pharmacological effects, including antitumor activity. Although it has potential as a therapeutic agent for cancer cells, the anti-senescence effects and detailed mechanism of action remain poorly understood in normal hepatic cells. We investigated the anticancer functions of fucoidan using HepG2 cells as well as the mechanisms mediating the anti-senescent acti...

BACKGROUND Germline mutations at the INK4a/p16 locus are implicated in several human cancer syndromes, including familial atypical multiple mole melanoma (FAMMM) syndrome, FAMMM-pancreatic cancer (FAMMM-PC) syndrome, and in familial head and neck cancer syndrome. METHODS We present an individual with a family history of melanoma and pancreatic cancer who had multiple dysplastic nevi, squamous...

Background: Oral cancer patients are found to have poor clinical outcome and high disease recurrence rate, in spite of an aggressive treatment regimen. The inactivation of INK4A/ARF loci is reported to be second to p53 inactivation in human cancers. The purpose of this study was to assess the prognostic significance of the molecular aberrations in the INK4A locus for effective identification of...

Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16(INK4a) tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) i...

Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV) infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise....