p16Ink4a inhibits histologic progression and angiogenic signaling in min colon tumors

Inducible re-expression of p16 in an orthotopic mouse model of pancreatic cancer inhibits lymphangiogenesis and lymphatic metastasis

“…The p16-mediated suppression of the angiogenic phenotype observed here is in excellent agreement with data obtained by inactivation of p16 in the MIN (Multiple Intestinal Neoplasia) mouse model of colon carcinogenesis (Gibson et al, 2003(Gibson et al, , 2005. Colonic tumours in MIN mice with additional p16 deletion revealed a strikingly increased vascularisation and slightly larger size as compared with p16-competent control animals.…”

INK4a deletion results in improved kidney regeneration and decreased capillary rarefaction after ischemia-reperfusion injury

“…Recent studies using p16 and p19 KO mice have demonstrated that loss of p16 results in increased tumor angiogenesis by contributing to increased VEGF levels, an effect that can be reversed by exogenous expression of p16 (6,7,27). The INK4a/ARF locus may also regulate angiogenesis by controlling growth and differentiation of pericytes.…”

“…Decreased INK4a/ARF expression may promote tissue repair and regeneration through multiple mechanisms, including induction of dedifferentiation and proliferation of mature cells as demonstrated in myotubes (18), prevention of apoptosis, and promotion of adult stem cell self-renewal as demonstrated in the central nervous system and hematopoietic cells (2). INK4a deletion has also been shown to result in increased tumor angiogenesis (6,8), suggesting another possible mechanism for promoting tissue repair.…”

Increased angiogenesis inCdk4R24C/R24C:Apc+/Minintestinal tumors

“…To establish a implicate a role for Cdk4 in angiogenesis. 13 These results were further supported by in vitro studies where inhibition of Cyclin D1 expression by anti-sense oligonucleotides as well as inhibition of Cdk4 kinase activity by a small molecule inhibitor, fascaplysin, was found to affect endothelial cell proliferation and blood vessel formation. 14,15 To demonstrate a direct role for Cdk4 in angiogenesis and to study the effects of Cdk4 activation on colorectal and intestinal tumor development, we crossed Cdk4 R24C/R24C mice with Apc +/Min mice and examined blood vessel formation in the intestinal tumors that developed in these compound mice.…”