J Korean Breast Cancer Soc.  2003 Sep;6(3):141-147. 10.4048/jkbcs.2003.6.3.141.

Expression of Chk2 and P53 in Sporadic Breast Cancer

• Song BJ
• Han SH
• Kim HS
• Kim CN
• Chang SH
• Seo YJ
• Jung SS

• KMID: 2006620
• DOI: http://doi.org/10.4048/jkbcs.2003.6.3.141

Abstract

PURPOSE
In response to DNA damage, Chk2 (CHEK2) is involved in cell cycle checkpoint. Chk2 is activated by the upstream ATM kinase and then directly phosphorylate p53 at serine 20. Other substrates for Chk2 are BRCA1, Cdc25A, Cdc25C, mdm2. Germ line mutations of Chk2 have been identified in Li-Fraumeni syndrome with normal p53 alleles. There are few reports on somatic mutations of Chk2 in osteosarcoma, lung cancer, breast cancer, testicular germ cell tumor, ovarian cancer. In this study, we have analyzed 30 breast cancer specimens to understand the relationship of Chk2 and P53 in the pathogenesis of sporadic breast cancer. METHODS: We performed an immunohistochemical studies for Chk2, P53 in the specimens from 30 breast cancer patients. We designed entire intronic primers and searched for Chk2mutations in 7 cases by DNA sequence analysis of the entire coding region. RESULTS: Seven of 30 (23.3%) breast cancers had reduced immuno-expression of Chk2, one of them (1/7, 14.3%) showed a p53 immuno-expression and all of them revealed no Chk2 mutation. CONCLUSION: Expression of Chk2 protein more reduced in breast cancer with no abnormal p53 immuno-expression. No Chk2 mutation was found in all of Chk2 reduced expression, we hypothesize that there may be a posttranscriptional/ posttranslational mechanism (s) in breast caner to downregulate Chk2 protein expression.

Keyword

Breast cancer; Chk2; P53

MeSH Terms

Alleles
Breast Neoplasms*
Breast*
Cell Cycle Checkpoints
Clinical Coding
DNA Damage
Germ Cells
Humans
Introns
Li-Fraumeni Syndrome
Lung Neoplasms
Neoplasms, Germ Cell and Embryonal
Osteosarcoma
Ovarian Neoplasms
Phosphotransferases
Sequence Analysis, DNA
Serine
Phosphotransferases
Serine