In this study, we investigated the relationship between SRPK2, Numb and p53 in the development of pancreatic cancer with or without chemical agent treatment in vitro.
We found that six novel tagging single-nucleotide polymorphisms (SNPs) (i.e, MAP2 rs35075084 T > deletion, PRKAG2 rs2727572 C > T and rs34852782 A > deletion, TP53rs9895829 A > G, and RPTOR rs62068300 G > A and rs3751936 G > C) were significantly associated with an increased PanC risk.
Accumulating evidence strongly suggests that p53 mutations contribute to the acquisition and/or maintenance of drug-resistant property of pancreatic cancer.
In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRAS<sup>G12D</sup> expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older).
In summary, our observations strongly indicated that, similarly to 2D monolayer culture, RUNX2 gene silencing increased GEM sensitivity of MiaPaCa‑2 spheres and highlighted the therapeutic potential of RUNX2 in pancreatic cancer with p53 mutation.
Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).
Detection of KRAS or p53 mutation in plasma is not an effective screening tool for pancreatic cancer because accumulation of multiple mutations is required for malignant transformation in the pancreas.
K-ras<sup>LSL-G12D/+</sup>:: p53<sup>LSL-R172H/+</sup>:: Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer that specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre.
Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC <i>in vitro</i> and <i>in</i><i>vivo</i>, an association that has not been reported to our knowledge.
Based on these findings, trichodermin is a potential therapeutic agent worthy of further development into a clinical trial candidate for treating cancer, especially the mutant p53pancreatic cancer.
In this study we examined the potential of three intrinsically fluorescent benzo[α]phenoxazines or BPZs (R=Cl, CH3, H) to induce cytotoxic autophagy in chemo and apoptosis-resistant, KRAS and p53 mutated pancreatic cancer model cell line, MIAPaCa-2.
The expression of alpha-enolase, Ki67 and p53 in pancreatic cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on the commercial tissue arrays.
In contrast, all animals with CI-lacking TP53 developed various subtypes of PC, including acinar cell carcinoma, ductal adenocarcinoma, sarcomatoid carcinoma and neuroendocrine tumors, and all died within 65 weeks.