Background: The Ink4a-Arf tumor suppressor locus encodes two growth inhibitors, p16 and Arf, both of which are also implicated as effectors in cellular senescence. Because human germline defects in the INK4A-ARF locus are associated with familial melanoma, melanocytes may have unusual INK4A-ARF functions or controls of cell senescence. Because senescence is believed to be an anticancer mechanis...

PURPOSE It is known that the pRb pathway cell-cycle inhibitor p16(INK4A) plays a significant role in cutaneous melanoma and that alteration of p16(INK4A), which resides within the 9p21-22 locus that also contains p15(INK4B) and p14(ARF), may occur in up to one third of uveal melanomas. The absence of TGFbeta responsiveness noted in cultured uveal melanoma cells also suggests that the TGFbeta pa...

Id1, a member of Id family of helix-loop-helix transcriptional regulatory proteins, is implicated in cellular senescence by repressing p16(INK4a) expression, but the mechanisms and cellular effects in human diploid fibroblasts remain unknown. Here we analyzed the patterns of p16(INK4a) and Id1 expression during the lifespan of 2BS cells and presented the inverse correlation between these two pr...

Cellular senescence suppresses cancer by preventing the proliferation of cells that experience potentially oncogenic stimuli. Senescent cells often express p16(INK4a), a cyclin-dependent kinase inhibitor, tumor suppressor, and biomarker of aging, which renders the senescence growth arrest irreversible. Senescent cells also acquire a complex phenotype that includes the secretion of many cytokine...

Glucocorticoids inhibit proliferation of many cell types, but the relationship between the glucocorticoid receptor (GR) and the proteins regulating cell cycle progression is not fully understood. We previously found that during fibrosarcoma (FS) progression, GR displays only modest transcriptional activity in the preneoplastic stages, whereas it is highly active in FS cells. Now, we report that...

BACKGROUND Development of squamous cell cancer of head and neck (SCCHN) is associated with human papillomavirus (HPV) infection, which in turn is closely related with expression of p16 INK4A. Loss of p16 INK4A expression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated p16 INK4A as a prognostic marker of treatment response and survival in our SCCHN patients with ...

OBJECTIVES/HYPOTHESIS To determine the prognostic influence of p16(INK4a) immunohistochemistry on the survival of resectable oropharyngeal carcinomas (OPSCC). STUDY DESIGN Retrospective pathologic evaluation of a prospective single-arm cohort study at a tertiary referral center. METHODS There were 48 patients with resectable OPSCC who consented for transoral robotic surgery (TORS) and banke...

BACKGROUND The p16(INK4a) gene methylation has been reported to be a major tumorigenic mechanism. METHODS We evaluated the methylation status of the p16(INK4a) genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16(INK4a) DN...

Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic ...

Osteosarcoma is one of the most common primary bone malignancies. Although there is a significant improvement of survival on osteosarcoma patients in the past decades, treatment of osteosarcoma is still unsatisfactory for the development of pulmonary metastasis. The potential prognostic value of p16(INK4a) in osteosarcoma has been investigated, however, the results from different studies were s...