## Abstract About 25–50% of women with Cowden disease, a syndrome associated with germ‐line mutations of the __PTEN__ gene (at 10q23), develop breast cancer (BC), but __PTEN__ mutations have been found in only 5% of sporadic BCs. However, 29–48% of BCs display loss of heterozygosity in 10q23, and a
PTEN promoter is methylated in a proportion of invasive breast cancers
✍ Scribed by Salma Khan; Takashi Kumagai; Jaimini Vora; Namrata Bose; Indu Sehgal; Phillip H. Koeffler; Shikha Bose
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- French
- Weight
- 143 KB
- Volume
- 112
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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. © 2004 Wiley‐Liss, Inc.
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