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The role of caspase 3 in producing cytokeratin 19 fragment (CYFRA21‐1) in human lung cancer cell lines
Author(s) -
Dohmoto Kazutaka,
Hojo Satoko,
Fujita Jiro,
Yang Yu,
Ueda Yutaka,
Bandoh Shuji,
Yamaji Yasufumi,
Ohtsuki Yuji,
Dobashi Naomi,
Ishida Toshihiko,
Takahara Jiro
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1082>3.0.co;2-t
Subject(s) - cytokeratin , lung cancer , cancer research , apoptosis , cancer , fragment (logic) , medicine , cell culture , cell , caspase , pathology , biology , oncology , programmed cell death , immunohistochemistry , genetics , computer science , programming language
The CYFRA 21‐1 assay, which detects cytokeratin 19 (CK19) fragment, is widely used as a tumor marker for lung cancer, particularly non‐small cell lung cancer. However, the reason that some lung cancer cell lines release CYFRA 21‐1 in culture supernatants and others do not remains unclear. We hypothesized that the release of CYFRA 21‐1 might be related to the expression of CK19 and caspase 3. In order to prove this, the quantities of mRNA for CK19 were evaluated by the competitive reverse transcriptase‐polymerase chain reaction (RT‐PCR). CK19 protein synthesis was also evaluated by Western blotting and immunohistochemistry, and the levels of CYFRA 21‐1 in the culture supernatant were measured by an immunoradiometric assay. The expression of mRNA for caspase 3 was evaluated by the RT‐PCR, and caspase 3 protein synthesis was also evaluated by immunohistochemistry. In 13 lung cancer cell lines, the amounts of mRNA for CK19 correlated with the levels of CYFRA 21‐1 in culture supernatants, results of Western blotting for CK19, and positivities of immunohistochemistry for CK19. In 5 cell lines that produced a significant amount of CYFRA 21‐1, the level of CYFRA 21‐1 correlated with the positivity of RT‐PCR for caspase 3 and immunohistochmistry for caspase 3. This suggests that caspase 3 played a role in the formation of CYFRA 21‐1. In addition, the specific inhibitor of caspase 3 significantly inhibited the release of CYFRA 21‐1 in culture supernatants. In conclusion, we demonstrate that caspase 3, which cleaves several intermediate filaments and carries out cell apoptosis, played an important role in producing CYFRA 21‐1 in human lung cancer cell lines. © 2001 Wiley‐Liss, Inc.