Active allele loss of the androgen receptor gene contributes to loss of androgen receptor expression in female breast cancers.
Given the importance of androgen and androgen receptor (AR) in the control of female breast growth and the potential association with female breast cancer, we evaluated the AR expression in 114 female breast cancers and further analyzed why AR expression was lost. Immunohistochemical analysis revealed that 14.1% (17/114) of the tumors lost the AR expression completely. To unravel the molecular mechanism for AR expression loss, we first analyzed the somatic mutations in exons 2 through 8 of the AR gene by PCR-SSCP, but no mutation was detected. As the CAG repeats within exon 1 are also microsatellite markers, we then analyzed whether allelic loss was present. Interestingly, 11 of the 17 AR-negative tumors were heterozygous and 9 of them showed allelic loss. The lost allele was further demonstrated to be the active one by X-chromosome inactivation analysis. To confirm the immunohistochemical results, Northern and Western blot hybridization was performed and neither AR mRNA nor protein was detected in these AR-negative tumors. Loss of the active AR allele was strongly correlated with the AR expression loss (P = 0.0005). We conclude that AR expression loss is attributed to the active allele loss of AR gene in female breast cancers. Our finding may be also crucial in predicting and influencing the response of breast cancer to endocrine therapy.
Shan
L
L
Department of Pathology, Department of Surgery, Wakayama Medical College, 811-1 Kimiidera, Wakayama City, Wakayama, 641-0012, Japan.
Yang
Q
Q
Nakamura
M
M
Nakamura
Y
Y
Mori
I
I
Sakurai
T
T
Kakudo
K
K
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D012333:RNA, Messenger; D011944:Receptors, Androgen