TITLE: CBP and Extracellular Matrix-Induced Apoptosis in p53(-) HMECs: A Model of Early Mammary Carcinogenesis PRINCIPAL INVESTIGATOR:

نویسنده

  • Victoria Seewaldt
چکیده

Methylation of the retinoic acid receptor-B2 (RARB2) P2promoter is hypothesized to be an important mechanismfor loss of RARB2 function during early mammary carci-nogenesis. The frequency of RARB2 P2 methylation wastested in (a) 16 early stage breast cancers and (b) 67random periareolar fine needle aspiration (RPFNA) samplesobtained from 38 asymptomatic women who were atincreased risk for breast cancer. Risk was defined as either(a) 5-year Gail risk calculation z1.7%; (b) prior biopsyexhibiting atypical hyperplasia, lobular carcinoma in situ , orductal carcinoma in situ ; or (c) known BRCA1/2 mutationcarrier. RARB2 P2 promoter methylation was assessed at tworegions, M3 ( 51 to 162 bp) and M4 (104-251 bp). In earlystage cancers, M4 methylation was observed in 11 of 16(69%) cases; in RPFNA samples, methylation was present atM3 and M4 in 28 of 56 (50%) and 19 of 56 (38%) cases,respectively. RPFNAs were stratified for cytologic atypiausing the Masood cytology index. The distribution ofRARB2 P2 promoter methylation was reported as a functionof increased cytologic abnormality. Methylation at both M3and M4 was observed in (a) 0 of 10 (0%) of RPFNAs withMasood scores of V10 (nonproliferative), (b) 3 of 20 (15%)with Masood scores of 11 to 12 (low-grade proliferative), (c)3 of 10 (30%) with Masood scores of 13 (high-gradeproliferative), and (d) 7 of 14 (50%) with Masood scores of14 of 15 (atypia). Results from this study indicate that theRARB2 P2 promoter is frequently methylated (69%) inprimary breast cancers and shows a positive associationwith increasing cytologic abnormality in RPFNA. (CancerEpidemiol Biomarkers Prev 2005;14(4):790–8)

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تاریخ انتشار 2006