Objective:To investigate the expression of the neu protein antigen in non-neoplastic, mammary epithelial cells o prepartum and actively lactating women.
Methods:Formalin-fixed, paraffin-embedded sections from breast biopsies obtained from four preparatum and seven postpartum, lactating women were stained for neu antigen with one commercially available monoclonal antibody (Ab-3), one commercially available polyclonal antibody (Ab-1), and another independently prepared polyclonal antibody (21N). Antigen competition experiments were carried out alongside as negative controls, and two strongly neu-positive breast carcinomas were included as positive controls.
Results:Membranes and cytoplasmic elements of two of the four preparation and four of the seven lactating specimens stained as strongly or nearly as strongly for neu antigen as did those of the breast carcinomas.
Conclusion:Our results demonstrate the expression of neu antigen by mammory epithelial cells just before and during lactation and suggest a possible role for this receptor in the lactational differentiation of the normal female breast.
1. Tooper YJ, Freeman CS. Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev1980;60:1049-1106.
2.
2. Vanderhaar BK. Regulation of development of the normal mammary gland by hormones and growth factors. In: Lippman ME, Dickson R, eds. Breast cancer cellular and molecular biology. Boston: Kluwer Academic Publishers, 1988:251-266.
3.
3. Quirk SJ, Slattery J, Funder JW. Mammary gland whey acidic protein: Ontogeny and changing patterns of steroid sensitivity. Mol Cel Endocrinol1989;66:135-141.
4.
4. Quirk SJ, Slattery J, Funder JW. 11 beta-hydroxysteroid dehydrogenase activity in the mammary gland. J Steroid Biochem1990;35:623-625.
5.
5. Hynes NE, Taverna D, Harwerth M, et al. Epidermal growth factor receptor, but not erbB2, activation prevents lactogenic hormone induction of the β-casein gene in mouse mammary epithelial cells. Mol Cell Biol1990;10:4027-4034.
6.
6. Lupu R, Colomar R, Zugmaier G, et al. Direct interaction of a ligand for the erbB-2 oncogene product with the EGF receptor and p185erbB2. Science1990;249:1552-1555.
7.
7. Coussens L, Yang-Feng TL, Liao YC, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science1985;230:1132-1139.
8.
8. Lupu R, Dickson RB, Lippman ME. The role of erbB-2 and its ligands in growth control of malignant breast epithelium. J Steroid Biochem Mol Biol1992;43:229-236.
9.
9. Huang SS, Huang JS. Purification and characterization of the neu/erb B2 ligand-growth factor from bovine kidney. J Biol Chem1992;267:11508-11512.
10.
10. Peles E, Bacus SS, Koski RA, et al. Isolation of the neu/HER-2 stimulatory ligand: A 44 kd glycoprotein that induces differentiation of mammaory tumor cells. Cell1992;69:205-216.
11.
11. Kacinski BM, Mayer AR, King BL, Carter D, Chambers SK. NEU protein overexpression in benign, borderline and malignant overian neoplasms. Gynecol Oncol1992;44:245-253.
12.
12. Haldane JS, Hird V, Hughes CM, Gullick WJ. c-erB-2 oncogene expression in ovarian cancer. J Pathol1990;162:231-237.
13.
13. Venter DJ, Tuzi NL, Kumar S, Gullick WJ. Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: Immunohistological assessment correlates with gene amplification. Lancet1987;ii:69-70.
14.
14. van de Vijver MJ, Peters JL, Mooi WJ, et al. Neu-protein overexpression in breast cancer. N Engl J Med1988;319:1239-1245.
15.
15. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncognene in human breast and ovarian cancer. Sscience1989;44:707-712.
16.
16. van de Vijver MJ, Mooi WJ, Wisman P, Peterse JL, Nusse R. Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA. Oncogene1988;2:175-178.
17.
17. Berger MS, Locher GW, Saurer S, et al. Correlation of c-erB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res1988;48; 1238-1243.
18.
18. Gusterson BA, Gullick WJ, Venter DJ, et al. Immunohistochemical localization of c-erbB-2 in human breast carcinomas. Mol Cell Probes1987;1:383-391.
19.
19. Thor AD, Schwartz LH, Koerner FC, et al. Analysis of c-erbB-2 expression in breast carcinomas with clinical follow-up. Cancer Res1989;49:7147-7152.
20.
20. Wright C. Expression of c-erbB-2 oncoprotein: A prognostic indicator in human breast cancer. Cancer Res1989;49:2087-2090.
21.
21. Maguire HC Jr, Jaworsky C, Cohen JA, Hellman M, Weiner DB, Greene MI. Distribution of neu (c-erbB-2) protein in human skin. J Invest Dermatol1989;92:786-790.
22.
22. DePotter CR, van Daele S, van de Vijver MJ, et al. The expression of the neu oncogene product in breast lesions and in normal fetal and adult human tissues. Histopathology1989;15:351-362.
23.
23. Berchuck A, Rodriguez G, Kinney RB, Soper JT. Overexpression of HER-2/neu in edometrial cancer is associated with advanced stage disease. Am J Obstet Gynecol1991;164:15-21.
24.
24. Boccaccio C, Gaudino G, Cilli M, Mondino A, Comoglio PM. Ligand-independent tyrosine phosphorylation of the receptor encoded by the c-neu oncogene. Growth Factors1991;5:233-242.
25.
25. Connelly PA, Stern DF. The epidermal growth factor receptor and the product of the NEU protooncogene are members of a receptor tyrosine phosphorylation cascade. Proc Natl Acad Sci USA1990;87;6054-6057.
26.
26. Bangalore L, Tannel AJ, Laudano AP, Stern DF. Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB2 and the EGF receptor. Proc Natl Acad Sci USA1992;89(23):11637-11641.
