The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study
Abstract Background Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal vesicles. Methods We explored the clinicopathological and prognostic significances of PGC mRNA using pathologica...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-06-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11020-z |
| _version_ | 1797806678378283008 |
|---|---|
| author | Ying E. Qian Yu Tao Sun Hang Xue Xue-rong Zhao Hua-chuan Zheng |
| author_facet | Ying E. Qian Yu Tao Sun Hang Xue Xue-rong Zhao Hua-chuan Zheng |
| author_sort | Ying E. |
| collection | DOAJ |
| description | Abstract Background Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal vesicles. Methods We explored the clinicopathological and prognostic significances of PGC mRNA using pathological and bioinformatics analyses. We generated PGC knockout and PGC-cre transgenic mice to observe the effects of PGC deletion and PTEN abrogation in PGC-positive cells on gastric carcinogenesis. Finally, we observed the effects of altered PGC expression on aggressive phenotypes by CCK8, Annexin V staining, wound healing and transwell assays and analyzed the partner proteins of PGC using co-IP (co-immunoprecipitation) and double fluorescence staining. Results PGC mRNA level was inversely correlated with the T and G stage and a short survival of gastric cancer (p < 0.05). PGC protein expression was negatively linked to lymph node metastasis, dedifferentiation, and low Her-2 expression of gastric cancer (p < 0.05). No difference in body weight or length was evident between wild-type (WT) and PGC knockout (KO) mice (p > 0.05), but PGC KO mice had a shorter survival than WT mice (p < 0.05). No gastric lesions were observed in the mucosa of the granular stomach in PGC KO mice, which displayed lower frequency and severity of gastric lesion than in WT mice after treated with MNU. Transgenic PGC-cre mice showed high cre expression and activity in the lung, stomach, kidney, and breast. Gastric cancer and triple-negative lobular breast adenocarcinoma were found in PGC-cre/PTENf/f mice with two previous pregnancies and breast feeding, but breast cancer was not seen in transgenic mice exposed to either estrogen or progesterone, or those with two previous pregnancies and no breast feeding. PGC suppressed proliferation, migration, invasion, and induced apoptosis, and interacted with CCNT1, CNDP2 and CTSB. Conclusion PGC downregulation was seen in gastric cancer, but PGC deletion resulted in resistance to chemically-induced gastric carcinogenesis. PGC expression suppressed the proliferation and invasion of gastric cancer cells possibly by interacting with CCNT1, CNDP2 and CTSB. Spontaneous triple-negative lobular adenocarcinoma and gastric cancer were seen in PGC-cre/PTENf/f mice, and the breast carcinogenesis was closely linked to pregnancy and breast feeding, but not to single exposure to estrogen or progesterone, or pregnancy. Limiting either pregnancy or breast feeding might help to prevent hereditary breast cancer. |
| first_indexed | 2024-03-13T06:10:56Z |
| format | Article |
| id | doaj.art-e8fee179e84947eeb445f60e34025e7a |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-13T06:10:56Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-e8fee179e84947eeb445f60e34025e7a2023-06-11T11:16:32ZengBMCBMC Cancer1471-24072023-06-0123111710.1186/s12885-023-11020-zThe relationship between pepsinogen C and gastric carcinogenesis: a transgene and population studyYing E.0Qian Yu1Tao Sun2Hang Xue3Xue-rong Zhao4Hua-chuan Zheng5Department of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical UniversityDepartment of Thoracic Surgery, The Affiliated Fourth Hospital of China Medical UniversityDepartment of Oncology, Liaoning Cancer HospitalDepartment of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical UniversityDepartment of Immunology, Basic Medicine College of Chengde Medical UniversityDepartment of Oncology and Central Laboratory, The Affiliated Hospital of Chengde Medical UniversityAbstract Background Pepsinogen C (PGC) is expressed in chief cells, fundic mucous neck cells, and pyloric gland cells of gastric epithelium and also in breast, prostate, lung, and seminal vesicles. Methods We explored the clinicopathological and prognostic significances of PGC mRNA using pathological and bioinformatics analyses. We generated PGC knockout and PGC-cre transgenic mice to observe the effects of PGC deletion and PTEN abrogation in PGC-positive cells on gastric carcinogenesis. Finally, we observed the effects of altered PGC expression on aggressive phenotypes by CCK8, Annexin V staining, wound healing and transwell assays and analyzed the partner proteins of PGC using co-IP (co-immunoprecipitation) and double fluorescence staining. Results PGC mRNA level was inversely correlated with the T and G stage and a short survival of gastric cancer (p < 0.05). PGC protein expression was negatively linked to lymph node metastasis, dedifferentiation, and low Her-2 expression of gastric cancer (p < 0.05). No difference in body weight or length was evident between wild-type (WT) and PGC knockout (KO) mice (p > 0.05), but PGC KO mice had a shorter survival than WT mice (p < 0.05). No gastric lesions were observed in the mucosa of the granular stomach in PGC KO mice, which displayed lower frequency and severity of gastric lesion than in WT mice after treated with MNU. Transgenic PGC-cre mice showed high cre expression and activity in the lung, stomach, kidney, and breast. Gastric cancer and triple-negative lobular breast adenocarcinoma were found in PGC-cre/PTENf/f mice with two previous pregnancies and breast feeding, but breast cancer was not seen in transgenic mice exposed to either estrogen or progesterone, or those with two previous pregnancies and no breast feeding. PGC suppressed proliferation, migration, invasion, and induced apoptosis, and interacted with CCNT1, CNDP2 and CTSB. Conclusion PGC downregulation was seen in gastric cancer, but PGC deletion resulted in resistance to chemically-induced gastric carcinogenesis. PGC expression suppressed the proliferation and invasion of gastric cancer cells possibly by interacting with CCNT1, CNDP2 and CTSB. Spontaneous triple-negative lobular adenocarcinoma and gastric cancer were seen in PGC-cre/PTENf/f mice, and the breast carcinogenesis was closely linked to pregnancy and breast feeding, but not to single exposure to estrogen or progesterone, or pregnancy. Limiting either pregnancy or breast feeding might help to prevent hereditary breast cancer.https://doi.org/10.1186/s12885-023-11020-zTransgenic mousePepsinogen CPTENGastric cancerBreast cancerChief cell |
| spellingShingle | Ying E. Qian Yu Tao Sun Hang Xue Xue-rong Zhao Hua-chuan Zheng The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study BMC Cancer Transgenic mouse Pepsinogen C PTEN Gastric cancer Breast cancer Chief cell |
| title | The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study |
| title_full | The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study |
| title_fullStr | The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study |
| title_full_unstemmed | The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study |
| title_short | The relationship between pepsinogen C and gastric carcinogenesis: a transgene and population study |
| title_sort | relationship between pepsinogen c and gastric carcinogenesis a transgene and population study |
| topic | Transgenic mouse Pepsinogen C PTEN Gastric cancer Breast cancer Chief cell |
| url | https://doi.org/10.1186/s12885-023-11020-z |
| work_keys_str_mv | AT yinge therelationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT qianyu therelationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT taosun therelationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT hangxue therelationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT xuerongzhao therelationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT huachuanzheng therelationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT yinge relationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT qianyu relationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT taosun relationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT hangxue relationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT xuerongzhao relationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy AT huachuanzheng relationshipbetweenpepsinogencandgastriccarcinogenesisatransgeneandpopulationstudy |