Expression of Biomarkers for Transformation in 7,12-Dimethylbenz[a]anthracene-Treated Mammary Epithelial-Cells

Garg, Alok; Suto, Akihiko; Mp, Osborne; Rc, Gupta; Telang, NT

doi:10.3892/ijo.3.2.185

Cited by 5 publications

(10 citation statements)

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“…Consistent with these models, the mouse mammary epithelial cell culture models exhibited induction of the multi-step carcinogenic process in response to treatment with the chemical carcinogen DMBA and also in response to the targeted overexpression of Ras and Myc oncogenes (20)(21)(22)(23)(24)(25). In 184-B5 cells, DMBA and BP, and in 184-B5/HER cells, targeted overexpression of the HER-2 oncogene induced carcinogenic transformation (20,25).…”

Section: Discussionmentioning

confidence: 79%

“…In 184-B5 cells, DMBA and BP, and in 184-B5/HER cells, targeted overexpression of the HER-2 oncogene induced carcinogenic transformation (20,25). In all these preclinical cell culture models the multi-step process of carcinogenic transformation is associated with a loss of homeostatic growth control and gain of carcinogenic risk, as evidenced by aberrant proliferation, accelerated cell cycle progression, downregulation of cell apoptosis, enhancement of AI in vitro and tumor development upon in vivo transplantation (20)(21)(22)(23)(24)(25). Thus, these models provide valuable mechanism-based approaches, complementing the existing in vivo models of transgenic mice and of athymic mice xeno-transplanted with human mammary carcinoma-derived cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…These initiated cells exhibit anchorage-independent colony formation in vitro and tumorigenic potential upon in vivo transplantation. The primary tumors derived from the pre-neoplasically transformed cells exhibit a persistent expression of the biomarkers for carcinogenic risk (22)(23)(24).…”

Section: Cell Culture Models and Mechanistic Biomarkersmentioning

confidence: 99%

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Epithelial cell culture models for the prevention and therapy of clinical breast cancer (Review)

Telang¹,

Katdare

2012

Oncol Lett

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Abstract. Clinical breast cancer progresses via a multi-step carcinogenic process wherein genetic, molecular, endocrine and dietary factors play significant roles in the pathogenesis, prevention and therapy of the disease. Preclinical cell culture models, expressing clinically relevant genetic and endocrine defects and exhibiting quantifiable cancer risk, may provide facile, clinically translatable approaches to identify molecular targets and susceptible mechanistic pathways for the efficacy of novel interventional approaches. This review summarizes laboratory investigations focused on i) developing murine and human mammary tissue-derived cell culture models; ii) optimizing mechanism-based quantitative endpoint biomarker assays specific for carcinogenic risk and preventive/ therapeutic efficacy; and iii) providing quantifiable proof-ofprinciple evidence for validation of the present cell culture approaches, capable of prioritizing efficacious lead compounds for subsequent in vivo animal studies and clinical trials for the prevention/therapy of breast cancer. Epithelial cell culture models are developed and characterized where the carcinogenic process is initiated by the targeted expression of clinically relevant oncogenes. The cell culture systems from mouse mammary tissue are in vitro approaches that complement the Ras and Myc transgenic mouse models. The human mammary tissue-derived systems are in vitro models for chemoendocrine, therapy-resistant, clinical, pre-invasive ER -/PR -/HER-2 + comedo ductal carcinoma in situ, ER + /PR + chemoendocrine therapy-responsive breast cancer and ER -/PR -/HER-2 -triplenegative chemoendocrine, therapy-resistant breast cancer. The oncogene-initiated phenotypes exhibit loss of homeostatic growth control, downregulation of cell apoptosis and gain of carcinogenic risk in vitro, as well as transplantable tumor development in vivo. Numerous mechanistically distinct, synthetic pharmacological agents, as well as naturally occurring dietary compounds, re-establish homeostatic growth control via cell cycle arrest and/or induction of cell apoptosis, downregulate oncogene-mediated cell signaling pathways, modulate the expression of numerous cell cycle regulatory and apoptosisspecific proteins and reduce carcinogenic risk in pre-neoplastic and carcinoma-derived cell culture models. These data validate the present cell culture approaches as novel, mechanism-based screens to evaluate and prioritize promising lead compounds for the prevention/therapy of clinical breast cancer.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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Epithelial cell culture models for the prevention and therapy of clinical breast cancer (Review)

Telang¹,

Katdare

2012

Oncol Lett

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“…The experiments in this study were conducted on in vitro models for human mammary (2,18,(31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…In these studies alteration in E2 metabolism was detected by specific and significant increase in C16a-hydroxylation, with a concomitant decrease in C2-hydroxylation pathways, while aberrant hyperproliferation was quantified by the relative extent of cell proliferation in anchoragedependent and anchorage-independent conditions of growth. Altered cellular metabolism of E2 and aberrant hyperproliferation, therefore, represent biochemical and cellular surrogate end point biomarkers for mammary carcinogenesis (4,9,(17)(18)(19)(20)(21) (2,4,(17)(18)(19). The tissue culture technology and biomarker assays established for the murine models have been optimized for human mammary tissue (4,22,23).…”

Section: Introductionmentioning

confidence: 99%

Estradiol Metabolism: An Endocrine Biomarker for Modulation of Human Mammary Carcinogenesis

Telang¹,

Katdare²,

Bradlow³

et al. 1997

Environmental Health Perspectives

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The natural estrogen 171-estradiol (E2) has a profound influence on proliferation and neoplastic transformation of mammary epithelium. The role of cellular metabolism of E2 in mammary carcinogenesis, however, remains to be elucidated. Explant culture and cell culture models developed from noncancerous human mammary tissue were used to examine modulation of E2 metabolism in response to treatment with prototype rodent mammary carcinogens and the ability of the naturally occurring phytochemical indole-3-carbinol (13C) to influence E2 metabolism and regulate aberrant proliferation. In the two models, treatment with the chemical carcinogens 7,12-dimethylbenz[alanthracene and benzolalpyrene altered the metabolism of E2 as determined from the radiometric (tritium release) and gas chromatography-mass spectrometry (GC-MS) assays. This alteration in E2 metabolism was accompanied by aberrant proliferation and abrogation of apoptosis as determined by the extent of replicative DNA synthesis, S-phase fraction and Sub Go (apoptotic) peak. Exposure of carcinogen-initiated cultures to 13C resulted in induction of C2-hydroxylation of E2 and of apoptosis and downregulation of hyperproliferation. Determination of altered cellular metabolism of E2 in response to initiators and modulators of carcinogenesis and evaluation of cell cycle related markers for proliferation and apoptosis may provide a mechanism-oriented approach to validate E2 metabolism as an endocrine biomarker for induction and prevention of human mammary carcinogenesis. -Environ Health Perspect 105(Suppl 3): 559-564 (1997)

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High-resolution anion-exchange and partition thin-layer chromatography for complex mixtures of 32P-postlabeled DNA adducts

Spencer-Beach

Beach

Gupta

1996

Journal of Chromatography B: Biomedical Sciences and Applicatio

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Expression of Biomarkers for Transformation in 7,12-Dimethylbenz[a]anthracene-Treated Mammary Epithelial-Cells

Cited by 5 publications

References 0 publications

Epithelial cell culture models for the prevention and therapy of clinical breast cancer (Review)

Epithelial cell culture models for the prevention and therapy of clinical breast cancer (Review)

Estradiol Metabolism: An Endocrine Biomarker for Modulation of Human Mammary Carcinogenesis

High-resolution anion-exchange and partition thin-layer chromatography for complex mixtures of 32P-postlabeled DNA adducts

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