Evidence map›Paper›PMID 20049202›Full record

ArticleEnvironmental health perspectives2009

Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype.

Lamia Benbrahim-Tallaa, Erik J Tokar, Bhalchandra A Diwan, Anna L Dill, Jean-François Coppin, Michael P Waalkes

Open access · diamondAbstract read
In one paragraph

Article in Environmental health perspectives, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.

  1. Association between dietary cadmium exposure and breast cancer risk: an updated meta-analysis of observational studies.Medical science monitor : international medical journal of experimental and clinical research · 2015
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Rethinking the microenvironment's role in chemical-induced malignancy.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Mechanisms of Heavy Metal Cadmium (Cd)-Induced Malignancy.Biological trace element research · 2025
    Review
  10. Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium.International journal of molecular sciences · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Lamia Benbrahim-TallaaInorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute (NCI) at National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
Erik J Tokar
Bhalchandra A Diwan
Anna L Dill
Jean-François Coppin
Michael P Waalkes
National Institutes of Health · USScience Applications International Corporation (United States) · US

Funding

Stem Cell ToxicologyZIAES102925 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI TOKAR, ERIK · 2010 to 2021
$25.3M
Mechanisms of Inorganic CarcinogenesisZIABC005488 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WAALKES, MICHAEL · 2009 to 2010
$2.5M
CCR NIH HHS HHSN261200800001CIntramural NIH HHSNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

backgroundBreast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation.

methodsCells were continuously exposed to low-level cadmium (2.5 μM) and checked in vitro and by xenograft study for signs of malignant transformation. Transformant cells were molecularly characterized by protein and transcript analysis of key genes in breast cancer.

resultsOver 40 weeks of cadmium exposure, cells showed increasing secretion of matrix metalloproteinase-9, loss of contact inhibition, increased colony formation, and increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated cells into mice produced invasive, metastatic anaplastic carcinoma with myoepithelial components. These cadmium-transformed breast epithelial (CTBE) cells displayed characteristics of basal-like breast carcinoma, including ER-alpha negativity and HER2 (human epidermal growth factor receptor 2) negativity, reduced expression of BRCA1 (breast cancer susceptibility gene 1), and increased CK5 (cytokeratin 5) and p63 expression. CK5 and p63, both breast stem cell markers, were prominently overexpressed in CTBE cell mounds, indicative of persistent proliferation. CTBE cells showed global DNA hypomethylation and c-myc and k-ras overexpression, typical in aggressive breast cancers. CTBE cell xenograft tumors were also ER-alpha negative.

conclusionsCadmium malignantly transforms normal human breast epithelial cells-through a mechanism not requiring ER-alpha-into a basal-like cancer phenotype. Direct cadmium induction of a malignant phenotype in human breast epithelial cells strongly fortifies a potential role in breast cancer.

Indexed as

Cell Transformation, NeoplasticAnimalsAromataseBreast NeoplasmsCadmiumCell Line, TumorEstrogen Receptor alphaFemaleHumansKeratin-5Membrane ProteinsMicePhenotypeAromataseCadmiumCKAP4 protein, humanEstrogen Receptor alphaKeratin-5Membrane Proteinsbasal-typebreast cancercadmiumestrogen receptormalignant transformation

Identifiers

PMID20049202
PMCPMC2799457
OpenAlexW2032166158

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.