Open AccessEpigenetic Regulation of the KAI1 Metastasis Suppressor Gene in Human Prostate Cancer Cell Lines
Author(s) -
Sekita Nobuyuki,
Suzuki Hiroyoshi,
Ichikawa Tomohiko,
Kito Hiroki,
Akakura Koichiro,
Igarashi Tatsuo,
Nakayama Tsuyoshi,
Watanabe Masatoshi,
Shiraishi Taizo,
Toyota Minoru,
Yoshie Osamu,
Ito Haruo
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb01185.x
Subject(s) - metastasis suppressor gene , epigenetics , metastasis , tumor suppressor gene , prostate cancer , cancer research , suppressor , metastasis suppressor , biology , chromoplexy , cancer , gene , prostate , cell culture , medicine , carcinogenesis , genetics , pca3
Expression of the KAI1 gene, a metastasis‐suppressor for prostate cancer, is reduced in all foci of prostatic metastasis. The altered regulatory mechanism is not strongly related to mutations or allelic losses of the KAI1 gene in prostate tumors. Since transcriptional silencing of genes has been found to be caused by epigenetic mechanisms, we have investigated the involvement of this epigenetic regulation of KAI1 expression in prostate cancers. The methylation status of the KAI1 promoter region was examined by restriction‐enzyme digestion and sequencing, after amplifying a 331‐bp fragment in the GC‐rich promoter region from 4 human prostate cancer cell lines treated with bisulfite. The same 4 cell lines were also exposed to various concentrations of the demethylating agent, 5‐aza‐2‐deoxycytidine (5‐AzaC) and/or the histone deacetylase inhibitor, trichostatin A (TSA). To clarify the influence of epigenetic modification on reduced KAI1 mRNA expression in the tumor cells, RT‐PCR and northern‐blot analyses were performed. Bisulfite‐sequencing data showed a few methylated CpG islands in the promoter. RT‐PCR analysis of 5‐AzaC and/or TSA‐treated cells indicated reversal of suppression of KAI1 transcription in two cell lines (PC‐3 and DU‐145), although the expression could not be detected by northern blots. From these results, it is suggested that epigenetic change is not the main mechanism of KAI1 down‐regulation, though there remains a possibility that methylation in a more upstream region might be associated with this regulation.