The CD44v6 epitope has been widely reported to be expressed in human mammary carcinomas, yet its prognostic significance is controversial and its function in mammary tumors and mammary glands is unknown. To begin to resolve these issues, we analysed in detail the normal postnatal expression patterns and regulation of the CD44v6 epitope in murine mammary glands. We demonstrate that significant CD44v6 epitope expression is first seen during puberty, and that after puberty CD44v6 epitope expression follows the estrous cycle. CD44v6 epitope expression is observed in the myoepithelium and also less widely in luminal epithelial cells. During lactation, CD44v6 epitope expression is turned off and reappears during involution. The CD44 variant isoform bearing the v6 epitope is CD44v1-v10. Using HC11, a mammary epithelial cell line with stem cell characteristics, and facilitated by the cloning of the murine CD44 promoter, we show that growth factors and hormones which regulate ductal growth and differentiation modulate CD44 transcription. Together our data suggest that the CD44v6 epitope is expressed in mammary epithelial stems cells and in lineages derived from these cells, and that CD44v6 expression is regulated in part by hormones and growth factors such as IGF-1 and EGF which regulate the growth and differentiation of the mammary epithelium. The function of these same growth factors and hormones is often perturbed in mammary carcinomas, and we suggest that CD44v6 expression in tumors reflects this perturbation. We conclude that the expression of the CD44v6 epitope observed in some mammary tumors reflects the stem cell origin of breast tumors, and that whether or not the CD44v6 epitope is expressed in a mammary tumor is determined by the differentiation status of the tumor cells.
CD44 expression and regulation during mammary gland development and function
L. Hebbard, A. Steffen, V. Zawadzki, C. Fieber, N. Howells, J. Moll, H. Ponta, M. Hofmann, J. Sleeman; CD44 expression and regulation during mammary gland development and function. J Cell Sci 15 July 2000; 113 (14): 2619–2630. doi: https://doi.org/10.1242/jcs.113.14.2619
Download citation file:
JCS Journal Meeting 2023: Imaging Cell Dynamics
Our 2023 Journal Meeting on ‘Imaging Cell Dynamics’ will be held from 14-17 May 2023 in Lisbon, Portugal. Due to popular demand, we can currently only accept applications for online attendance. Apply now to attend this meeting virtually. Registration deadline: 31 March.
Call for papers: Cell and Tissue Polarity
We are welcoming submissions for our next special issue, which will focus on ‘Cell and tissue polarity’ and will be guest edited by David Bryant. Submission deadline: 15 July.
Editorial: Publishing where it matters
Editor-in-Chief Michael Way outlines Journal of Cell Science’s plans for the upcoming year and introduces Seema Grewal as our new Executive Editor.
preLights 5th Birthday webinar
preLights, our preprint highlighting service, is celebrating its 5th birthday this year. To mark the occasion, join us online on 14 March 2023 at 16:00 GMT for a discussion, led by four preLights alumni, on how to identify and navigate the challenges and opportunities while shaping your career as an early-career researcher.
Cell Scientists to Watch
As a community-focused journal, Journal of Cell Science is keen to support the next generation of cell biologists. Check out Cell Scientists to Watch, our interview series featuring talented researchers who have recently set up their own labs.