Vascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPARalpha is a nuclear receptor controlling lipid metabolism and inflammation, but its role in the regulation of SMC growth remains to be established. Here, we show that PPARalpha controls SMC cell-cycle progression at the G1/S transition by targeting the cyclin-dependent kinase inhibitor and tumor suppressor p1...

Our previous studies indicated that p16 suppresses breast cancer angiogenesis and metastasis, and downregulates VEGF gene expression by neutralizing the transactivation of the VEGF transcriptional factor HIF-1α. Hypoxia stimulates tumor malignant progression and induces HIF-1α. Because p16 neutralizes effect of HIF-1α and attenuates tumor metastatic progression, we intended to investigate wheth...

It is well known that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of the p16 gene; however, whether or not the inactivation is associated with the clinical significance of multiple myeloma (MM) remains elusive. A meta-analysis was conducted to quantitatively determine the role of the p16 hypermethylation in the clinical significance of MM. We demonstrated ...

HBP1 is a sequence-specific DNA-binding transcription factor with many important biological roles. It activates or represses the expression of some specific genes during cell growth and differentiation. Previous studies have exhibited that HBP1 binds to p16(INK4A) promoter and activates p16(INK4A) expression. We found that trichostatin A (TSA), an inhibitor of HDAC (histone deacetylase), induce...

Cyclin-dependent kinase inhibitor p16(INK4a) is implicated in replicative senescence, cell immortalization, and tumor generation. However, the mechanism regulating its overexpression in senescent cells is unknown. We used the enhanced green fluorescent protein reporter system to scan regulatory elements in the upstream region of p16(INK4a). The results of 5'-deletion studies indicated that the ...

BACKGROUND Tumor human papillomavirus (HPV) status is an important prognostic factor in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Prognostic value in recurrent and/or metastatic (R/M) disease remains to be confirmed. This retrospective analysis of the EXTREME trial, comparing chemotherapy plus cetuximab with chemotherapy first line in R/M SCCHN, investigated ...

OBJECTIVE A genomic region near the CDKN2A locus, encoding p16(INK4a), has been associated to type 2 diabetes and atherosclerotic vascular disease, conditions in which inflammation plays an important role. Recently, we found that deficiency of p16(INK4a) results in decreased inflammatory signaling in murine macrophages and that p16(INK4a) influences the phenotype of human adipose tissue macroph...

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. ...

BACKGROUND The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has been rising in recent years. Given the clinical impact of HPV/p16 positivity in OPSCC, identifying surrogate markers of this disease early in the diagnostic work-up of these patients could improve patient care. METHODS Demographic, pathologic, staging and PET-CT data from patients ...

Telomere attrition in primary human fibroblasts induces replicative senescence accompanied by activation of the p53 and p16(INK4a)/RB tumor suppressor pathways. Although the contribution of p53 and its target, p21, to telomere-driven senescence have been well established, the role of p16(INK4a) is controversial. Attempts to dissect the significance of p16(INK4a) in response to telomere shorteni...