Claudin 7 as a possible novel molecular target for the treatment of pancreatic cancer.

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.

• Authors: Norimitsu Okui, Yuko Kamata, Yukiko Sagawa, Akiko Kuhara, Kazumi Hayashi, Tadashi Uwagawa, Sadamu Homma, Katsuhiko Yanaga
• Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] (Pancreatology) Vol. 19 Issue 1 Pg. 88-96 (Jan 2019) ISSN: 1424-3911 [Electronic] Switzerland
• PMID: 30416041 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Chemical References

• CLDN7 protein, human
• Claudins
• RNA, Small Interfering

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Claudins (genetics, metabolism)
• G1 Phase Cell Cycle Checkpoints
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Mice
• Neoplasms, Experimental
• Oligonucleotide Array Sequence Analysis
• Pancreatic Neoplasms (drug therapy)
• RNA, Small Interfering