Evidence map›Paper›PMID 22279424›Full record

ArticleJournal of carcinogenesis2011

A block in lineage differentiation of immortal human mammary stem / progenitor cells by ectopically-expressed oncogenes.

Xiangshan Zhao, Gautam K Malhotra, Hamid Band, Vimla Band

Abstract read
In one paragraph

Article in Journal of carcinogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Xiangshan ZhaoDepartment of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA.
Gautam K Malhotra
Hamid Band
Vimla Band

Funding

TYROSINE KINASE REGULATION VIA PROTEIN DEGRADATIONR01CA087986 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2000 to 2015
$4.2M
MOLECULAR CONTROL OF EGF RECEPTOR DOWN-REGULATIONR01CA099163 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2003 to 2012
$3.7M
Targeting Endocytic Recycling of EGF Receptor in Cancer R01CA105489 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2004 to 2014
$3.0M
A novel regulator of p53 functionR01CA096844 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2002 to 2011
$2.7M
High Capacity Nanocarriers for Cancer ChemotherapeuticsU01CA151806 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KABANOV, ALEXANDER V · 2010 to 2014
$2.0M
Ecd as a regulator of cell cycle and breast oncogenesisR01CA144027 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2011 to 2015
$1.6M
ErbB2 Downregulation Through HSP90 InhibitionR01CA116552 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, HAMID · 2007 to 2011
$1.4M
NCI NIH HHS R01 CA087986NCI NIH HHS R01 CA096844NCI NIH HHS R01 CA099163NCI NIH HHS R01 CA105489NCI NIH HHS R01 CA116552NCI NIH HHS R01 CA144027NCI NIH HHS U01 CA151806
6 · The paper itself

Abstract

introductionEmerging evidence suggests a direct role of cancer stem cells (CSCs) in the development of breast cancer. In vitro cellular models that recapitulate properties of CSCs are therefore highly desirable. We have previously shown that normal human mammary epithelial cells (hMECs) immortalized with human telomerase reverse transcriptase (hTERT) possess properties of mammary stem / progenitor cells. MATERIALS AND

methodsIn the present study, we used this cell system to test the idea that other known hMEC-immortalizing oncogenes (RhoA, HPVE6, HPVE7, p53 mutant, and treatment with γ-radiation), share with hTERT, the ability to maintain mammary stem / progenitor cells.

resultsThe results presented here demonstrate that similar to hMECs immortalized with hTERT, all hMEC cell lines immortalized using various oncogenic strategies express stem / progenitor cell markers. Furthermore, analyses using 2D and 3D culture assays demonstrate that all the immortal cell lines retain their ability to self-renew and to differentiate along the luminal lineage. Remarkably, the stem / progenitor cell lines generated using various oncogenic strategies exhibit a block in differentiation along the myoepithelial lineage, a trait that is retained on hTERT-immortalized stem / progenitors. The inability to differentiate along the myoepithelial lineage could be induced by ectopic mutant p53 expression in hTERT-immortalized hMEC.

conclusionsOur studies demonstrate that stem / progenitor cell characteristics of hMECs are maintained upon immortalization by using various cancer-relevant oncogenic strategies. Oncogene-immortalized hMECs show a block in their ability to differentiate along the myoepithelial lineage. Abrogation of the myoepithelial differentiation potential by a number of distinct oncogenic insults suggests a potential explanation for the predominance of luminal and rarity of myoepithelial breast cancers.

Indexed as

Immortalizationluminal differentiationmyoepithelial differentiationself-renewalstem cell

Identifiers

PMID22279424
PMCPMC3263028

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Registered trials

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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.