期刊
CANCER RESEARCH
卷 66, 期 1, 页码 29-33出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-05-2508
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- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R21ES011672] Funding Source: NIH RePORTER
- NIEHS NIH HHS [R21 ES011672] Funding Source: Medline
The HER-2/neu gene is amplified and overexpressed in 20% to 30% of invasive breast carcinomas and is associated with increased metastatic potential and less tamoxifen sensitivity. We generated the DNA methylation profiles of 143 human breast tumors and found significant differences in HER-2/neu expression and DNA methylation of five genes. For three of these five genes [PGR (coding for the progesterone receptor), HSD17B4 (coding for type 4 17-beta-liydroxysteroid dehydrogenase, an enzyme that mainly degrades active 17-beta-estradiol into inactive metabolites), and CDH13 (coding for H-cadherin)] it higher prevalence of DNA methylation in HER-2/neu-positive cancers was confirmed lit an independent set of microdissected primary breast cancers. DNA methylation was not only present in cancer cells but also in the tumor stroma fraction. Of the isolated fractions in HER-2/neu-positive versus -negative cancers, 27.1% versus 10.5%, respectively, showed DNA methylation of the five genes (P = 0.011, Fisher's exact test.). lit Her-2++/+++. breast cancers, HSD17B4 mRNA expression was inversely associated with HSD17B4 methylation (P = 0.04). These data support the view that lit addition to HER-2/neu-associated signaling, epigenetic changes in cancer as well as lit tumor stroma cells might attribute to the specific biological features of HER-2/neu-positive cancers.
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