PURPOSE: To analyze epigenetic regulation of two related genes, insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) and IGFBPL1, and its significance as a determinant of clinical phenotypes in human breast cancer. EXPERIMENTAL DESIGN: We have investigated the expression and epigenetic regulation of IGFBP-rP1 and IGFBPL1 in human breast cancer cell lines and primary and metastatic carcinomas. RESULTS: Expression of IGFBP-rP1 and IGFBPL1 is down-regulated in breast cancer cell lines. Aberrant methylation in the CpG islands of each gene correlates well with loss of expression at the mRNA level. Analysis of methylation in DNA isolated from human primary breast tumors showed that methylation in either gene was associated with a worse overall survival (OS; P=0.008) and disease-free survival (DFS) following surgery (P=0.04) and worse DFS following adjuvant chemotherapy (P=0.01). Methylation of IGFBP-rP1 alone was associated with a trend toward decreased OS (P=0.10) and decreased DFS (P=0.25). Methylation in IGFBPL1 was clearly associated with worse OS (P=0.001) and DFS (P<0.0001). Methylation in either IGFBP-rP1 or IGFBPL1 was significantly associated with nodal disease (P<0.001). CONCLUSIONS: Expression of IGFBP-rP1 and IGFBPL1 is regulated by aberrant hypermethylation in breast cancer, implying that inactivation of these genes is involved in the pathogenesis of this malignancy. Analysis of methylation of these genes may have utility in prediction of clinical phenotypes, such as nodal disease and response to chemotherapy.
PURPOSE: To analyze epigenetic regulation of two related genes, insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) and IGFBPL1, and its significance as a determinant of clinical phenotypes in human breast cancer. EXPERIMENTAL DESIGN: We have investigated the expression and epigenetic regulation of IGFBP-rP1 and IGFBPL1 in human breast cancer cell lines and primary and metastatic carcinomas. RESULTS: Expression of IGFBP-rP1 and IGFBPL1 is down-regulated in breast cancer cell lines. Aberrant methylation in the CpG islands of each gene correlates well with loss of expression at the mRNA level. Analysis of methylation in DNA isolated from human primary breast tumors showed that methylation in either gene was associated with a worse overall survival (OS; P=0.008) and disease-free survival (DFS) following surgery (P=0.04) and worse DFS following adjuvant chemotherapy (P=0.01). Methylation of IGFBP-rP1 alone was associated with a trend toward decreased OS (P=0.10) and decreased DFS (P=0.25). Methylation in IGFBPL1 was clearly associated with worse OS (P=0.001) and DFS (P<0.0001). Methylation in either IGFBP-rP1 or IGFBPL1 was significantly associated with nodal disease (P<0.001). CONCLUSIONS: Expression of IGFBP-rP1 and IGFBPL1 is regulated by aberrant hypermethylation in breast cancer, implying that inactivation of these genes is involved in the pathogenesis of this malignancy. Analysis of methylation of these genes may have utility in prediction of clinical phenotypes, such as nodal disease and response to chemotherapy.
Authors: Liangjing Wang; Xian Wang; Xiaojia Wang; Pan Jie; Haiqi Lu; Shengjie Zhang; Xiaoying Lin; Emily Ky Lam; Yan Cui; Jun Yu; Hongchuan Jin Journal: Am J Cancer Res Date: 2010-11-10 Impact factor: 6.166
Authors: Zhaohui Du; Niels Weinhold; Gregory Chi Song; Kristin A Rand; David J Van Den Berg; Amie E Hwang; Xin Sheng; Victor Hom; Sikander Ailawadhi; Ajay K Nooka; Seema Singhal; Karen Pawlish; Edward S Peters; Cathryn Bock; Ann Mohrbacher; Alexander Stram; Sonja I Berndt; William J Blot; Graham Casey; Victoria L Stevens; Rick Kittles; Phyllis J Goodman; W Ryan Diver; Anselm Hennis; Barbara Nemesure; Eric A Klein; Benjamin A Rybicki; Janet L Stanford; John S Witte; Lisa Signorello; Esther M John; Leslie Bernstein; Antoinette M Stroup; Owen W Stephens; Maurizio Zangari; Frits Van Rhee; Andrew Olshan; Wei Zheng; Jennifer J Hu; Regina Ziegler; Sarah J Nyante; Sue Ann Ingles; Michael F Press; John David Carpten; Stephen J Chanock; Jayesh Mehta; Graham A Colditz; Jeffrey Wolf; Thomas G Martin; Michael Tomasson; Mark A Fiala; Howard Terebelo; Nalini Janakiraman; Laurence Kolonel; Kenneth C Anderson; Loic Le Marchand; Daniel Auclair; Brian C-H Chiu; Elad Ziv; Daniel Stram; Ravi Vij; Leon Bernal-Mizrachi; Gareth J Morgan; Jeffrey A Zonder; Carol Ann Huff; Sagar Lonial; Robert Z Orlowski; David V Conti; Christopher A Haiman; Wendy Cozen Journal: Blood Adv Date: 2020-01-14
Authors: Leonardo Pignataro; Florence P Varodayan; Lindsay E Tannenholz; Petr Protiva; Neil L Harrison Journal: Brain Behav Date: 2013-02-06 Impact factor: 2.708