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Event: 1066

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Promotion, Sine oculis homeobox 1 positive progenitor cells in endometrium

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Promotion, SIX1 positive progenitor cells in endometrium

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
precursor cell

Organ term

Organ term
endometrium epithelium

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
cell proliferation	homeobox protein SIX1	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Early-life ER agonism and endometrial adenosquamous carcinoma via SIX1 expression	KeyEvent	Travis Karschnik (send email)	Under Development: Contributions and Comments Welcome

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
Homo sapiens	Homo sapiens	High	NCBI
Mus musculus	Mus musculus	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Embryo	High
Fetal	High
Adult	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Female	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

An increase in SIX1 positive progenitor cells is observed at the cellular level, in this case, occuring in the endometrium. While there are functional distinctions, progenitor cells are any cell that has the capacity to proliferate. The term is commonly used to indicate a cell that is in the process of cell division or has the potential to enter the cell cycle (Zemans and Downey 2016).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Measuring SIX1-positive cells takes place via detecting the presence of the SIX1 protein or its mRNA using molecular biology techniques. Including the following:

Immunohistochemistry
Immunofluorescence
Flow cytometry
Western blotting
qRT-PCR

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Taxonomic Applicability

Increases in SIX1 positive progenitor cells in the endometrium are restricted to mammals as they are the only species group with that organ.

Lifestage Applicability

Endometrial SIX1 positive progenitor cells have been measured during embryonic development, as part of normal processes, and in adulthood in response to injury or cancer contexts.

Sex Applicability

This event is restricted to the endometrium and is therefore female specific.

References

List of the literature that was cited for this KE description. More help

Coletta, R. D., McCoy, E. L., Burns, V., Kawakami, K., McManaman, J. L., Wysolmerski, J. J., & Ford, H. L. (2010). Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis. BMC developmental biology, 10(1), 4.

McCoy, E. L., Iwanaga, R., Jedlicka, P., Abbey, N. S., Chodosh, L. A., Heichman, K. A., ... & Ford, H. L. (2009). Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition. The Journal of clinical investigation, 119(9), 2663-2677

Micalizzi, D. S., Christensen, K. L., Jedlicka, P., Coletta, R. D., Barón, A. E., Harrell, J. C., ... & Ford, H. L. (2009). The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-β signaling. The Journal of clinical investigation, 119(9), 2678-2690.

Rachel L. Zemans, Gregory P. Downey, 15 - Injury and Repair, Editor(s): V. Courtney Broaddus, Robert J. Mason, Joel D. Ernst, Talmadge E. King, Stephen C. Lazarus, John F. Murray, Jay A. Nadel, Arthur S. Slutsky, Michael B. Gotway, Murray and Nadel's Textbook of Respiratory Medicine (Sixth Edition), W.B. Saunders, 2016, Pages 251-260.e9, ISBN 9781455733835, https://doi.org/10.1016/B978-1-4557-3383-5.00015-4. (https://www.sciencedirect.com/science/article/pii/B9781455733835000154)