Expression of p21waf1/Cip1 in stromal fibroblasts of primary breast tumors

Human Molecular Genetics
George TrimisAthanasios G Papavassiliou

Abstract

During carcinogenesis, stromal fibroblasts undergo certain changes in concert with their neoplastic neighbors, an interaction that progressively leads to a cancer-associated state. However, despite the increasing appreciation of the importance of stromal/tumor interactions in the progression of cancer, little is known about the factors responsible for regulating the crosstalk between stromal fibroblasts and neoplastic cells. Here we show that the stage of the disease in primary human breast lesions affects p21 expression in the fibroblasts. In stromal fibroblasts of benign fibroadenomas, p21 exhibits a periductal pattern of staining, which is abolished in malignant adenocarcinomas in which p21 immunopositivity exhibits a mosaic pattern that eventually is abolished in more aggressive types of the disease. In order to address the role of fibroblasts' p21 in tumorigenesis, we have reconstituted MCF7 human breast cancers in mice, with fibroblasts differing in the p21 status. These experiments showed that p21 deficiency in stromal fibroblasts accelerates tumor growth through cell non-autonomous mechanism(s). In addition, even a transient, siRNA-mediated p21 suppression in fibroblasts sufficiently stimulates MCF7 and MDA-MB-231 growt...Continue Reading

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Citations

Nov 2, 2012·Cancer Metastasis Reviews·Yan MaoJianhua Wang
May 12, 2011·Cellular Oncology (Dordrecht)·Ioulia ChatzistamouAthanasios G Papavassiliou
Mar 15, 2013·Genes & Cancer·Elena FarmakiHippokratis Kiaris
Jul 1, 2014·Cancers·Kim De VeirmanKarin Vanderkerken
Jun 20, 2014·Carcinogenesis·Tomer CooksMoshe Oren
Aug 26, 2014·Nature Cell Biology·Masayuki ShimodaRama Khokha
Mar 19, 2016·Journal of Cancer Research and Clinical Oncology·Hailong FuWenrong Xu
Jun 17, 2009·International Journal of Cancer. Journal International Du Cancer·Patricia Bortman RozenchanMaria Mitzi Brentani
Dec 9, 2014·Nucleus·Henry D HerceM Cristina Cardoso
Nov 17, 2009·Seminars in Cell & Developmental Biology·Jair BarMoshe Oren
Jul 10, 2009·Molecular Cancer·David G MollevíAlberto Villanueva
Feb 12, 2015·Endocrine-related Cancer·Chrysovalantou MihailidouHippokratis Kiaris
Feb 12, 2015·Endocrine-related Cancer·Chrysovalantou MihailidouHippokratis Kiaris
May 18, 2016·Oncogene·E FarmakiH Kiaris
Sep 12, 2018·The Journal of Clinical Investigation·Yingying WangJianhua Wang
Mar 30, 2018·Frontiers in Oncology·Maria Kalli, Triantafyllos Stylianopoulos
Apr 21, 2016·Molecular Oncology·Konstantinos G SidiropoulosGeorge M Yousef
Mar 14, 2020·Pancreas·Francesco Di Maggio, Karim Hussien El-Shakankery

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