scholarly journals Loss of p53 protein during radiation transformation of primary human mammary epithelial cells.

1994 ◽  
Vol 14 (4) ◽  
pp. 2468-2478 ◽  
Author(s):  
D E Wazer ◽  
Q Chu ◽  
X L Liu ◽  
Q Gao ◽  
H Safaii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
P53 Protein ◽  
Neoplastic Transformation ◽  
Mammary Epithelial ◽  
G1 Arrest ◽  
Protein Loss ◽  
The Third ◽  
Human Mammary Epithelial

The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells.

Loss of p53 protein during radiation transformation of primary human mammary epithelial cells

1994 ◽  
Vol 14 (4) ◽  
pp. 2468-2478
Author(s):  
D E Wazer ◽  
Q Chu ◽  
X L Liu ◽  
Q Gao ◽  
H Safaii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
P53 Protein ◽  
Neoplastic Transformation ◽  
Mammary Epithelial ◽  
G1 Arrest ◽  
Protein Loss ◽  
The Third ◽  
Human Mammary Epithelial

The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells.

scholarly journals Overexpression of ErbB2 enhances ethanol-stimulated intracellular signaling and invasion of human mammary epithelial and breast cancer cells in vitro

Oncogene ◽  
2003 ◽  
Vol 22 (34) ◽  
pp. 5281-5290 ◽  
Author(s):  
Cuiling Ma ◽  
Hong Lin ◽  
Stephen S Leonard ◽  
Xianglin Shi ◽  
Jianping Ye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Mammary Epithelial ◽  
Human Mammary Epithelial

scholarly journals Distinct Oncogenic Transcriptomes in Human Mammary Epithelial Cells Infected With Cytomegalovirus

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandy Haidar Ahmad ◽  
Sébastien Pasquereau ◽  
Ranim El Baba ◽  
Zeina Nehme ◽  
Clara Lewandowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Low Risk ◽  
Human Mammary Epithelial Cells ◽  
Mammosphere Formation ◽  
Human Mammary Epithelial

Human cytomegalovirus is being recognized as a potential oncovirus beside its oncomodulation role. We previously isolated two clinical isolates, HCMV-DB (KT959235) and HCMV-BL (MW980585), which in primary human mammary epithelial cells promoted oncogenic molecular pathways, established anchorage-independent growth in vitro, and produced tumorigenicity in mice models, therefore named high-risk oncogenic strains. In contrast, other clinical HCMV strains such as HCMV-FS, KM, and SC did not trigger such traits, therefore named low-risk oncogenic strains. In this study, we compared high-risk oncogenic HCMV-DB and BL strains (high-risk) with low-risk oncogenic strains HCMV-FS, KM, and SC (low-risk) additionally to the prototypic HCMV-TB40/E, knowing that all strains infect HMECs in vitro. Numerous pro-oncogenic features including enhanced expression of oncogenes, cell survival, proliferation, and epithelial-mesenchymal transition genes were observed with HCMV-BL. In vitro, mammosphere formation was observed only in high-risk strains. HCMV-TB40/E showed an intermediate transcriptome landscape with limited mammosphere formation. Since we observed that Ki67 gene expression allows us to discriminate between high and low-risk HCMV strains in vitro, we further tested its expression in vivo. Among HCMV-positive breast cancer biopsies, we only detected high expression of the Ki67 gene in basal tumors which may correspond to the presence of high-risk HCMV strains within tumors. Altogether, the transcriptome of HMECs infected with HCMV clinical isolates displays an “oncogenic gradient” where high-risk strains specifically induce a prooncogenic environment which might participate in breast cancer development.

scholarly journals Attenuation of TGF-β signaling suppresses premature senescence in a p21-dependent manner and promotes oncogenic Ras-mediated metastatic transformation in human mammary epithelial cells

2012 ◽  
Vol 23 (8) ◽  
pp. 1569-1581 ◽  
Author(s):  
Shu Lin ◽  
Junhua Yang ◽  
Abdel G. Elkahloun ◽  
Abhik Bandyopadhyay ◽  
Long Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Dependent Manner ◽  
Human Mammary Epithelial Cells ◽  
Major Player ◽  
Human Mammary Epithelial ◽  
Basal Like Breast Cancer

The molecular mechanisms that drive triple-negative, basal-like breast cancer progression are elusive. Few molecular targets have been identified for the prevention or treatment of this disease. Here we developed a series of isogenic basal-like human mammary epithelial cells (HMECs) with altered transforming growth factor-β (TGF-β) sensitivity and different malignancy, resembling a full spectrum of basal-like breast carcinogenesis, and determined the molecular mechanisms that contribute to oncogene-induced transformation of basal-like HMECs when TGF-β signaling is attenuated. We found that expression of a dominant-negative type II receptor (DNRII) of TGF-β abrogated autocrine TGF-β signaling in telomerase-immortalized HMECs and suppressed H-Ras-V12–induced senescence-like growth arrest (SLGA). Furthermore, coexpression of DNRII and H-Ras-V12 rendered HMECs highly tumorigenic and metastatic in vivo in comparison with H-Ras-V12–transformed HMECs that spontaneously escaped H-Ras-V12–induced SLGA. Microarray analysis revealed that p21 was the major player mediating Ras-induced SLGA, and attenuated or loss of p21 expression contributed to the escape from SLGA when autocrine TGF-β signaling was blocked in HMECs. Furthermore, knockdown of p21 also suppressed H-Ras-V12–induced SLGA. Our results identify that autocrine TGF-β signaling is an integral part of the cellular anti-transformation network by suppressing the expression of a host of genes, including p21-regulated genes, that mediate oncogene-induced transformation in basal-like breast cancer.

scholarly journals Bovine Leukemia Virus Non-Productive Infection of Human Mammary Epithelial Cells (MCF10A)

2020 ◽  
pp. 1-4
Author(s):  
Maria Carolina Ceriani ◽  
Lucía Martínez Cuesta ◽  
Pamela A Lendez ◽  
Maureen A Sheahan ◽  
Raymond RR Rowland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Mammary Epithelial ◽  
Productive Infection ◽  
Mammary Tissue ◽  
Viral Gene ◽  
Epithelial Cell Line ◽  
Human Mammary Epithelial

Bovine leukemia virus (BLV) is a retrovirus that causes lymphosarcoma in cattle. Some researchers suggest that BLV could be related to breast cancer development, however, evidence that the virus can infect the human counterpart is lacking. For that reason, the objective of this study was to infect in vitro a human mammary epithelial cell line (MCF10A) with BLV. The results suggest that the infection is non-productive, since only a fragment of the viral gene pol was detected in the cellular DNA. These results are consistent with previous studies, where fragments of different BLV genes were found in human mammary tissue. Future studies should investigate whether this non-productive infection can be associated with human breast cancer.

scholarly journals YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie Mei ◽  
Yan Liu ◽  
Xinqian Yu ◽  
Leiyu Hao ◽  
Tao Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Transcriptional Regulator ◽  
Expression Levels ◽  
Functional Roles ◽  
Normal Tissues ◽  
Rhoa Activation ◽  
Promote Cell Migration

AbstractDishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

scholarly journals The ETS Transcription Factor ESE-1 Transforms MCF-12A Human Mammary Epithelial Cells via a Novel Cytoplasmic Mechanism

2004 ◽  
Vol 24 (12) ◽  
pp. 5548-5564 ◽  
Author(s):  
Jason D. Prescott ◽  
Karen S. N. Koto ◽  
Meenakshi Singh ◽  
Arthur Gutierrez-Hartmann
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Nuclear Localization ◽  
Human Breast Cancer ◽  
Mammary Epithelial Cells ◽  
Cell Transformation ◽  
Mammary Epithelial ◽  
Human Breast ◽  
Human Mammary Epithelial

ABSTRACT Several different transcription factors, including estrogen receptor, progesterone receptor, and ETS family members, have been implicated in human breast cancer, indicating that transcription factor-induced alterations in gene expression underlie mammary cell transformation. ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine- and aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly expressed in human breast cancer and trans-activates epithelium-specific gene promoters in transient transfection assays. While it has been presumed that ETS factors transform mammary epithelial cells via their nuclear transcriptional functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation. Deletion of transcriptional regulatory or nuclear localization domains does not impair ESE-1-mediated transformation, whereas fusing the simian virus 40 T-antigen nuclear localization signal to various ESE-1 constructs, including the SAR domain alone, inhibits their transforming capacity. Finally, we show that the nuclear localization of ESE-1 protein induces apoptosis in nontransformed mammary epithelial cells via a transcription-dependent mechanism. Together, our studies reveal two distinct ESE-1 functions, apoptosis and transformation, where the ESE-1 transcription activation domain contributes to apoptosis and the SAR domain mediates transformation via a novel nonnuclear, nontranscriptional mechanism. These studies not only describe a unique ETS factor transformation mechanism but also establish a new paradigm for cell transformation in general.

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