title: PTEN promoter is methylated in a proportion of invasive breast cancers.
abstract: The PTEN protein is a negative regulator of the Akt pathway, leading to suppression of apoptosis and increased cell survival. Its role as a tumor-suppressor gene has been adequately substantiated, and homozygous mutations have been demonstrated in familial and sporadic cancers. In breast cancers, expression of PTEN protein is lost/reduced in 38% of cases. Somatic mutations are, however, rarely found. Our study was therefore designed to determine if differential methylation of the PTEN promoter region has a role in the transcriptional inactivation of the gene in invasive breast carcinomas. A total of 44 samples of invasive human breast cancer, 5 breast cancer cell lines and 16 samples of normal human breast tissue from young and elderly women were studied for methylation of the PTEN promoter by methylation-specific PCR and PTEN protein expression by immunohistochemistry. PTEN methylation occurred in 34% of breast cancers, and 60% of these samples were associated with loss of PTEN protein. Analyzed from a different perspective, 34% of breast cancers had reduced expression of PTEN and 60% had a methylated PTEN promoter. None of the breast cancer cell lines and normal breast tissues showed methylation. In summary, methylation of the PTEN promoter leads to PTEN inactivation in a subset of human breast cancers.
authors.affiliation: Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Salma
authors.initials: S
authors.lastname: Khan
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumagai
authors.forename: Jaimini
authors.initials: J
authors.lastname: Vora
authors.forename: Namrata
authors.initials: N
authors.lastname: Bose
authors.forename: Indu
authors.initials: I
authors.lastname: Sehgal
authors.forename: Phillip H
authors.initials: PH
authors.lastname: Koeffler
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human