Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer.
The relation between thyroid status and diseases and cancer is unclear. No detailed analysis of thyroid hormone receptor (TR) expression in human breast cancer has been reported. We have analysed the expression and mutational status of the TRalpha1, encoded by the c-erbA proto-oncogene, TRbeta1 and TRbeta2 isoforms in 70 sporadic breast cancers. Alterations in the RNA level of TRbeta1, TRalpha1, or both were found in a number of patients. No expression of TRbeta2 RNA was detected. Western blotting analysis confirmed the differences in expression at the protein level in those cases where sufficient tumor sample was available. Additionally, tumor-specific truncated TRbeta1 RNA was found in six patients. Strikingly, three transcripts shared the same breakpoint. Only one tumor carried the corresponding deletion at the genomic DNA level, suggesting that the remaining abnormal TRbeta1 transcripts are aberrant splicing products. Though no significant correlation was found between TRbeta1 alteration and any clinical parameter, it showed a tendency to associate with early age of onset (<50 years). Our results reveal specific alterations in the expression of TRbeta and TRalpha genes in a subset of breast cancer patients, suggesting that deregulation of thyroid hormone target genes may be involved in the generation of this neoplasia.
Silva
José M
JM
Department of Medical Oncology, Clínica Puerta de Hierro, E-28035 Madrid, Spain.
Domínguez
Gemma
G
González-Sancho
José M
JM
García
José M
JM
Silva
Javier
J
García-Andrade
Carmen
C
Navarro
Antonia
A
Muñoz
Alberto
A
Bonilla
Félix
F
D000328:Adult; D000483:Alleles; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018776:Genes, erbA; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D000090063:Proto-Oncogene Mas; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis*; D017384:Sequence Deletion; D013963:Thyroid Hormones / Q000502:physiology
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones