Intrinsic Cooperation between p16INK4a and p21Waf1/Cip1 in the Onset of Cellular Senescence and Tumor Suppression In vivo

Abstract

Although the p16 INK4a

Anti-proliferation Effects of Interferon-gamma on Gastric Cancer Cells

“…Transfection of the dsRNA of p21 in lung cancer cells upregulated p21 expression, suppressed cell growth and enhanced sensitivity to cisplatin, an important anticancer drug (Wei et al, 2010). p21Waf1/Cip1 and p16INK4a may synergistically facilitate the aging of skin cancer cells and play an anti-tumor role (Takeuchi et al, 2010). We found CDKN1A upregulated in gastric cancer cells exposed to IFN-γ.…”

“…Of 7 genes examined, 4 are closely associated with the cell cycle: cyclin B1 (Yuan et al, 2004;Yuan et al, 2006), cyclin-dependent protein kinase 1 (CDK1) (Li et al, 2000;Xiao et al, 2009), and mitogen-activated protein kinase 12 (MAPK12) (Marinissen et al, 2001;Tortorella et al, 2003;Hou et al, 2010) were downregulated and cyclin-dependent kinase inhibitor 1A (CDKN1A) was upregulated (Cazzalini et al, 2010;Gao et al, 2010;Takeuchi et al, 2010;Wei et al, 2010). Other genes closely associated with cell proliferation and migration were differentially regulated: carcinoembryonic antigenrelated cell adhesion molecule 6 (CEACAM6) (Duxbury et al, 2004;Mahata et al, 2006;Poola et al, 2006;Blumenthal et al, 2007;Lasa et al, 2008) and Wilms tumor 1 (WT1) (Sakamoto et al, 2009;Rushing et al, 2010) were downregulated, and metastasis suppressor 1 (MTSS) was upregulated (Figure 2) (Liu et al, 2010).…”

Late Onset Neuropathy with Spontaneous Clinical Remission in Mice Lacking the POZ Domain of the Transcription Factor Myc-interacting Zinc Finger Protein 1 (Miz1) in Schwann Cells

“…Besides its role in cell cycle regulation, p21 Cip1 has been identified as a crucial player in the establishment and maintenance of senescence (54,55). To this end, we prepared sciatic nerve fragments and performed whole-mount SA ␤-galactosidase staining to probe for this senescence marker (13).…”

Epigallocatechin-3-gallate and trichostatin A synergistically inhibit human lymphoma cell proliferation through epigenetic modification of p16INK4a

“…In addition to regulating the CDK4-Rb pathway, p16 INK4a decreases eukaryotic elongation factor (eEF) 1A2 expression, reducing cancer cell proliferation (4). It also induces cellular senescence in a cooperative manner with p21 Waf1/Cip1 , which was confirmed in double-knockout mice that were more susceptible to skin tumor formation (5). Moreover, enforced expression of p16 INK4a in cisplatin-resistant non-small cell lung cancer cells increased their sensitivity to low cisplatin concentrations (6).…”