Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland

Institutes of ^*Anatomy and ^∥Internal Medicine, School of Medicine, University of Ancona, Via Tronto 10/A, 60020 Ancona, Italy; ^‡Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215; ^§Center for Study and Research on Obesity, Laboratorio Interdisciplinare Tecnologie Avanzate Vialba, Luigi Sacco Hospital, Via G. B. Grassi 74, 20157 Milan, Italy; and ^¶University of Medicine and Pharmacy, Stradã Petru Rares̊ 4, 200349 Craiova 1100, Romania

Communicated by Elizabeth D. Hay, Harvard Medical School, Boston, MA, October 15, 2004 (received for review July 6, 2004)

Abstract

Mammalian breast adipose tissue is replaced by a milk-secreting gland during pregnancy; the reverse process takes place upon interruption of lactation. Morphological and bromodeoxyuridine studies provide indirect evidence that mouse mammary adipocytes transform into secretory epithelial cells during pregnancy and revert to adipocytes after lactation. By using the Cre-loxP recombination system we show that the mammary gland of whey acidic protein (WAP)-Cre/R26R mice, in which secretory epithelial cells express the lacZ gene during pregnancy, contains labeled adipocytes during involution. Conversely, adipocyte P2-Cre/R26R mice, in which adipocytes are labeled before pregnancy, contain labeled secretory epithelial cells during pregnancy. We conclude that reversible adipocyte-to-epithelium and epithelium-to-adipocyte transdifferentiation occurs in the mammary gland of adult mice during pregnancy and lactation.

Footnotes

↵ ** To whom correspondence should be addressed at: Institute of Normal Human Morphology, School of Medicine, University of Ancona, Via Tronto 10/A, 60020 Ancona, Italy. E-mail: cinti{at}univpm.it.
↵ † M.M., A.G., and M.C.Z. contributed equally to this work.
Author contributions: M. Morroni, A.G., M.C.Z., R.B., R.D.M., C.T., C.P., M.M.L., and M. Marelli performed research; M. Morroni, A.G., M.C.Z., B.B.K., E.N., and S.C. analyzed data; A.G. and S.C. wrote the paper; B.B.K. contributed new reagents/analytic tools; and S.C. designed research.
Abbreviations: WAP, whey acidic protein; aP2, adipocyte-binding protein 2.