Add like
Add dislike
Add to saved papers

Cell lineage tracing links ERα loss in Erbb2-positive breast cancers to the arising of a highly aggressive breast cancer subtype.

HER2-positive (HER2+ ) breast cancers (BrCs) contain approximately equal numbers of ERα+ HER2+ and ERα- HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+ HER2+ BrCs could lose ERα to become ERα- HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCre RFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+ RFP+ Erbb2+ and ERα- RFP- Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+ RFP+ Erbb2+ cells and ERα- RFP- Erbb2+ cells in these lesions were rare. The subsequently developed ductal carcinomas in situ had 64% slow-proliferating ERα+ RFP+ Erbb2+ cells, 15% fast-proliferating ERα- RFP+ Erbb2+ cells derived from ERα+ RFP+ Erbb2+ cells, and 20% fast-proliferating ERα- RFP- Erbb2+ cells. The advanced tumors had mostly ERα- RFP+ Erbb2+ and ERα- RFP- Erbb2+ cells and only a very small population of ERα+ RFP+ Erbb2+ cells. In ERα- RFP+ Erbb2+ cells, GATA3 and FoxA1 decreased expression and ERα promoter regions became methylated, consistent with the loss of ERα expression. Lung metastases consisted of mostly ERα- RFP+ Erbb2+ cells, a few ERα- RFP- Erbb2+ cells, and no ERα+ RFP+ Erbb2+ cells. The high metastatic capacity of ERα- RFP+ Erbb2+ cells was associated with ERK1/2 activation. These results show that the slow-proliferating, nonmetastatic ERα+ RFP+ Erbb2+ cells progressively lose ERα during tumorigenesis to become fast-proliferating, highly metastatic ERα- RFP+ Erbb2+ cells. The ERα- Erbb2+ BrCs with an ERα+ origin are more aggressive than those ERα- Erbb2+ BrCs with an ERα- origin, and thus, they should be distinguished and treated differently in the future.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app