Cytokeratin 19 promoter directs the expression of Cre recombinase in various epithelia of transgenic mice

Abstract

Cytokeratin 19 (K19) is expressed in various differentiated cells, including gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here, we generated a transgenic mouse line, K19-Cre, in which the expression of Cre recombinase was controlled by the promoter of K19. To test the tissue distribution and excision activity of Cre recombinase, K19-Cre transgenic mice were bred with Rosa26 reporter strain and a mouse strain that carries PTEN conditional alleles (PTENLoxp/Loxp). At mRNA level, Cre was strongly expressed in the stomach, lung and intestine, while in stomach, lung, and liver at protein level. The immunoreactivity to Cre was strongly observed the cytoplasm of gastric, bronchial and intestinal epithelial cells. Cre activity was detectable in gastric, bronchial and intestinal epithelial cells, according to LacZ staining. In K19-Cre/PTEN Loxp/Loxp mice, PTEN was abrogated in stomach, intestine, lung, liver and breast, the former two of which were verified by in situ PCR. There appeared breast cancer with PTEN loss. These data suggest that K19 promoter may be a useful tool to study the pathophysiological functions of cytokeratin 19-positive cells, especially gastrointestinal epithelial cells. Cell specificity of neoplasia is not completely attributable to the cell-specific expression of oncogenes and cell-specific loss of tumor suppressor genes.

CK7/CK19 index: A potential prognostic factor for postoperative intrahepatic cholangiocarcinoma patients

“…Cytokeratins (CKs) are intermediate filament proteins mainly expressed in epithelial cells and composed of type I (CK9‐20) and type II (CK1‐8) cytokeratins . Previous studies have demonstrated that CKs played a critical role in maintaining epithelial barriers, regulating innate immunity, intracellular signaling, cell adhesion, epithelial cell proliferation, and differentiation .…”

“…Cytokeratins (CKs) are intermediate filament proteins mainly expressed in epithelial cells and composed of type I (CK9-20) and type II (CK1-8) cytokeratins. 5 Previous studies have demonstrated that CKs played a critical role in maintaining epithelial barriers, regulating innate immunity, intracellular signaling, cell adhesion, epithelial cell proliferation, and differentiation. 6 Among them, cytokeratin 7 (CK7)is expressed in various tissue types, such as intestine crypt, pancreatic ducts, mammary gland ducts, and liver bile ducts but absent in hepatocytes.…”

The roles of PTEN expression in gastric cancer: a bibliometric, meta and bioinformatics analysis

“…Therefore, we performed a meta-and bioinformatics analysis about PTEN expression in gastric cancer at both mRNA and protein levels in the following work. Gastric precancerous lesions appear between gastric epithelium and adenocarcinoma, and are divided into adenomatous, regenerative, crysptal and globoid dysplasia [50]. Jang et al [51] reported that nuclear PTEN expression was gradually down-regulated during colorectal mucosa-adenoma-adenocarcinomametastasis sequence.…”

The roles of maspin expression in gastric cancer: a meta- and bioinformatics analysis

“…According to the literature [ 52 ], precancerous lesions appear from gastric epithelium to adenocarcinoma, including adenomatous, regenerative, crysptal or globoid dysplasia. Consistent with the data about breast, colonic, bladder and gastric cancers [ 15 , 27 ], we found down-regulated maspin expression in gastric cancer, compared with gastric mucosa or dysplasia in the present study, suggesting that maspin hypoexpression contributed to gastric carcinogenesis as a late event.…”