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The Establishment of Esophageal Precancerous Lesion Model by Using p53 Conditional Knockout Mouse in Esophageal Epithelium.

ABSTRACT: Understanding the molecular mechanisms of precancerous lesion of esophageal cancer is beneficial for early diagnosis and early treatment. The deletion of p53 gene is common in esophageal cancer, but its pathogenesis is still unclear. An animal model is urgently needed to study the mechanisms of esophageal cancer and p53 deficiency. KO mice (p53flox/flox.ED-L2-Cre+/-) and the corresponding control Loxp mice (p53flox/flox.ED-L2-Cre-/-) were obtained by crossing between the p53flox/flox mice and ED-L2-Cre+/- mice. Methylbenzylnitrosamine (NMBA) was injected subcutaneously to induce esophageal precancerous lesion of these two groups of mice. Hematoxylin and eosin staining analysis was performed to evaluate the number and extent of esophageal precancerous lesions in KO mice and Loxp mice at the 16th and 48th weeks. Immunohistochemistry analysis was used to detect the change of Ki67, P21, Bcl-2, and Bax proteins. The number and extent of esophageal precancerous lesions in KO mice were significantly increased compared with the control at the 16th and 48th weeks under the induction of NMBA. The Ki67, P21, Bcl-2, and Bax proteins also had cancer-related pathological characteristics. These results suggest that the esophageal precancerous lesion model was established under the combined effect of p53 gene deletion in esophageal epithelium and NMBA, which could provide a new esophageal precancerous lesion model to explore the mechanism of precancerous lesions.

SUBMITTER: Zhu L

PROVIDER: S-EPMC7003290 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Establishment of Esophageal Precancerous Lesion Model by Using p53 Conditional Knockout Mouse in Esophageal Epithelium.

Zhu Lili L Xu Yanyan Y Chen Xinhuan X Qin Jiace J Niu Tingting T Zhu Yanyan Y Jiang Yanan Y Zhao Simin S Liu Kangdong K Lu Jing J Jin Ge G Ma Junfen J Dong Ziming Z Zhao Jimin J

BioMed research international 20200125

Understanding the molecular mechanisms of precancerous lesion of esophageal cancer is beneficial for early diagnosis and early treatment. The deletion of p53 gene is common in esophageal cancer, but its pathogenesis is still unclear. An animal model is urgently needed to study the mechanisms of esophageal cancer and p53 deficiency. KO mice (p53flox/flox.ED-L2-Cre+/-) and the corresponding control Loxp mice (p53flox/flox.ED-L2-Cre-/-) were ...[more]

PMID: 32047812

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Project description:Epithelial ovarian cancer is the most lethal gynecological malignancy among US women. The etiology of this disease, although poorly understood, may involve the ovarian surface epithelium or the epithelium of the fallopian tube fimbriae as the progenitor cell. Disruptions in the transforming growth factor beta (TGFβ) pathway and p53 are frequently found in chemotherapy-resistant serous ovarian tumors. Transgenic mice expressing a dominant negative form of Smad2 (Smad2DN), a downstream transcription factor of the TGFβ signaling pathway, targeted to tissues of the reproductive tract were created on a FVB background. These mice developed epithelium-lined inclusion cysts, a potential precursor lesion to ovarian cancer, which morphologically resembled oviductal epithelium but exhibited protein expression more closely resembling the ovarian surface epithelium. An additional genetic "hit" of p53 deletion was predicted to result in ovarian tumors. Tissue specific deletion of p53 in the ovaries and oviducts alone was attempted through intrabursal or intraoviductal injection of Cre-recombinase expressing adenovirus (AdCreGFP) into p53 (flox/flox) mice. Ovarian bursal cysts were detected in some mice 6 months after intrabursal injection. No pathological abnormalities were detected in mice with intraoviductal injections, which may be related to decreased infectivity of the oviductal epithelium with adenovirus as compared to the ovarian surface epithelium. Bitransgenic mice, expressing both the Smad2DN transgene and p53 (flox/flox), were then exposed to AdCreGFP in the bursa and oviductal lumen. These mice did not develop any additional phenotypes. Exposure to AdCreGFP is not an effective methodology for conditional deletion of floxed genes in oviductal epithelium and tissue specific promoters should be employed in future mouse models of the disease. In addition, a novel phenotype was observed in mice with high expression of the Smad2DN transgene as validated through qPCR analysis, characterized by teratoma-like lesions implicating Smad signaling in teratoma development.

Dataset Information

The Establishment of Esophageal Precancerous Lesion Model by Using p53 Conditional Knockout Mouse in Esophageal Epithelium.

Publications

The Establishment of Esophageal Precancerous Lesion Model by Using <i>p53</i> Conditional Knockout Mouse in Esophageal Epithelium.

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