1. Claudin 7 as a possible novel molecular target for the treatment of pancreatic cancer
- Author
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Norimitsu Okui, Katsuhiko Yanaga, Yuko Kamata, Sadamu Homma, Akiko Kuhara, Tadashi Uwagawa, Kazumi Hayashi, and Yukiko Sagawa
- Subjects
endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Population ,Cell ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,RNA, Small Interfering ,education ,Claudin ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,Gene knockdown ,education.field_of_study ,Hepatology ,Cell growth ,Kinase ,business.industry ,Gastroenterology ,Neoplasms, Experimental ,Cell cycle ,medicine.disease ,G1 Phase Cell Cycle Checkpoints ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Claudins ,Cancer research ,030211 gastroenterology & hepatology ,business - Abstract
Background/objectives Pancreatic cancer consists of various subpopulations of cells, some of which have aggressive proliferative properties. The molecules responsible for the aggressive proliferation of pancreatic cancer may become molecular targets for the therapies against pancreatic cancer. Methods From a human pancreatic cancer cell line, MIA PaCa-2, MIA PaCa-2-A cells with an epithelial morphology and MIA PaCa-2-R cells with a non-epithelial morphology were clonogenically isolated by the limiting dilution method. Gene expression of these subpopulations was analyzed by DNA microarray. Gene knockdown was performed using siRNA. Results Although the MIA PaCa-2-A and MIA PaCa-2-R cells displayed the same DNA short tandem repeat (STR) pattern identical to that of the parental MIA PaCa-2 cells, the MIA PaCa-2-A cells were more proliferative than the MIA PaCa-2-R cells both in culture and in tumor xenografts generated in immunodeficient mice. Furthermore, the MIA PaCa-2-A cells were more resistant to gemcitabine than the MIA PaCa-2-R cells. DNA microarray analysis revealed a high expression of claudin (CLDN) 7 in the MIA PaCa-2-A cells, as opposed to a low expression in the MIA PaCa-2-R cells. The knockdown of CLDN7 in the MIA PaCa-2-A cells induced a marked inhibition of proliferation. The MIA PaCa-2-A cells in which CLDN7 was knocked down exhibited a decreased expression of phosphorylated extracellular signal-regulated kinase (p-Erk)1/2 and G1 cell cycle arrest. Conclusions CLDN7 may be expressed in the rapidly proliferating and dominant cell population in human pancreatic cancer tissues and may be a novel molecular target for the treatment of pancreatic cancer.
- Published
- 2019