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Characterization of a newly established human pancreatic carcinoma cell line, UK Pan‐1
Author(s) -
Fralix Kimberly D.,
Ahmed Mansoor M.,
Mattingly Cynthia,
Swiderski Carol,
McGrath Patrick C.,
Venkatasubbarao Kolaparthi,
Kamada Nanao,
Mohiuddin Mohammed,
Strodel William E.,
Freeman James W.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000501)88:9<2010::aid-cncr5>3.0.co;2-5
Subject(s) - microbiology and biotechnology , cell culture , biology , cancer research , transforming growth factor , growth factor , mutation , pancreatic cancer , cell growth , fluorescence in situ hybridization , gene , receptor , genetics , cancer , endocrinology , chromosome
BACKGROUND A highly tumorigenic cell line designated as UK Pan‐1 was established in a surgically removed human pancreatic adenocarcinoma and characterized as having many of the genotypic and phenotypic alterations commonly found in pancreatic tumors. METHODS The cell line was characterized by its morphology, growth rate in monolayer culture and soft agar, tumorigenicity in nude mice, and chromosomal analysis. Furthermore, the status of p53, Ki‐ras mutation and transforming growth factor (TGF)‐β receptor expression were determined. The characteristics of UK Pan‐1 were compared with those of other commonly used pancreatic carcinoma cell lines. RESULTS Quiescent UK Pan‐1 cells could be stimulated to proliferate in growth factor free nutrient media, indicating a growth factor independent phenotype. UK Pan‐1 cells grew in soft agar and rapidly formed tumors in nude mice. This cell line possesses a mutation at codon 12 of the c–Ki‐ras‐2 gene that is commonly found in pancreatic carcinoma. Fluorescence in situ hybridization showed that two alleles of p53 tumor suppressor gene were present in UK Pan‐1. However, sequencing analysis revealed a mutation in one allele at exon 8, codon 273 (G to A; Arg to His). Additional growth assays indicated that the cell line was insensitive to negative growth regulation induced by exogenous TGF‐β. Molecular analysis of the TGF‐β signaling pathway showed that UK Pan‐1 did not express appreciable levels of the TGF‐β receptor type I, II, or III mRNAs, but did express DPC4 mRNA. Karyotype analysis revealed an 18q21 deletion indicating a possible loss of heterozygosity for DPC4, as well as other chromosomal deletions and rearrangements. CONCLUSIONS This study indicates that UK Pan‐1 is a highly tumorigenic cell line possessing a molecularly complex pattern of mutations that may be used as a model to further the understanding of the mechanisms responsible for the development of pancreatic carcinoma. Cancer 2000;88:2010–21. © 2000 American Cancer Society.