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The molecular causes of low ATM protein expression in breast carcinoma; promoter methylation and levels of the catalytic subunit of DNA‐dependent protein kinase
Author(s) -
Treilleux I,
Chapot B,
Goddard S,
Pisani P,
Angèle S,
Hall J
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02726.x
Subject(s) - dna pkcs , dna methylation , biology , cancer research , epigenetics , microbiology and biotechnology , protein kinase a , methylation , breast carcinoma , immunohistochemistry , protein subunit , gstp1 , dna , kinase , cancer , breast cancer , gene , gene expression , genetics , immunology , genotype
Aims: To investigate whether aberrant methylation of the ATM promoter or loss of the catalytic subunit of DNA‐dependent protein kinase (DNA‐PKcs) may be the underlying causes of reduced ATM protein levels often seen in breast tumours. Methods and results: Methylation‐specific polymerase chain reaction was used to determine the ATM promoter status and DNA‐PKcs levels were measured by immunohistochemistry. None of the 74 invasive carcinomas (ICs) studied showed ATM promoter hypermethylation, whereas promoter methylation of CDKN2A/p16 (1.8%) and GSTP1 (15.8%) was detected. Of 92 ICs examined, 68 had reduced DNA‐PKcs levels, supporting previous findings that alterations in double‐strand break repair are associated with breast cancer pathogenesis. Although no association was found between the DNA‐PKcs and ATM scores for the series of 92 tissues and 22/24 tissues with normal DNA‐PKcs had reduced ATM, 29 tumours showed low expression of both DNA‐PKcs and ATM compared with normal tissues. Conclusions: No evidence was found that the reduction in ATM protein levels seen in breast carcinoma is the result of epigenetic silencing. However, cross‐regulation between DNA‐PKcs and ATM may be a possible cause in a subset of tumours and warrants further investigation.