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. 1992 Nov 2;119(4):997–1002. doi: 10.1083/jcb.119.4.997

The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis

PMCID: PMC2289688  PMID: 1429845

Abstract

We have cloned from a mouse placenta cDNA library a mouse homologue of the human stromelysin-3 (ST3) cDNA, which codes for a putative matrix metalloproteinase expressed in breast carcinomas. The ST3 protein is well conserved between humans and mice, and the pattern of ST3 gene expression is similar in both species, and shows expression in the placenta, in the uterus, and during limb bud morphogenesis. We show that the ST3 gene can also be expressed in the normal mouse mammary gland. ST3 gene expression was not detected during mammary growth, neither in virgin nor in pregnant mice, but was specifically observed during postlactating involution of the gland, an apoptotic process associated with intense extracellular matrix remodeling. ST3 transcripts were found in fibroblasts immediately surrounding degenerative ducts, suggesting that ST3 gene expression may be associated with the basement membrane dissolution, which occurs during mammary gland involution. Since the ST3 gene is also specifically expressed in fibroblastic cells surrounding invasive neoplastic cells of breast carcinomas, we suggest that ST3 is implicated in extracellular matrix remodeling processes common to mammary apoptosis and breast cancer progression.

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Selected References

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  1. Basset P., Bellocq J. P., Wolf C., Stoll I., Hutin P., Limacher J. M., Podhajcer O. L., Chenard M. P., Rio M. C., Chambon P. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990 Dec 20;348(6303):699–704. doi: 10.1038/348699a0. [DOI] [PubMed] [Google Scholar]
  2. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  3. Coleman S., Silberstein G. B., Daniel C. W. Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor. Dev Biol. 1988 Jun;127(2):304–315. doi: 10.1016/0012-1606(88)90317-x. [DOI] [PubMed] [Google Scholar]
  4. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  5. Flaumenhaft R., Rifkin D. B. Extracellular matrix regulation of growth factor and protease activity. Curr Opin Cell Biol. 1991 Oct;3(5):817–823. doi: 10.1016/0955-0674(91)90055-4. [DOI] [PubMed] [Google Scholar]
  6. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  7. Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Liotta L. A., Stetler-Stevenson W. G. Metalloproteinases and cancer invasion. Semin Cancer Biol. 1990 Apr;1(2):99–106. [PubMed] [Google Scholar]
  9. Martinez-Hernandez A., Fink L. M., Pierce G. B. Removal of basement membrane in the involuting breast. Lab Invest. 1976 May;34(5):455–462. [PubMed] [Google Scholar]
  10. Matrisian L. M. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990 Apr;6(4):121–125. doi: 10.1016/0168-9525(90)90126-q. [DOI] [PubMed] [Google Scholar]
  11. Ossowski L., Biegel D., Reich E. Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Cell. 1979 Apr;16(4):929–940. doi: 10.1016/0092-8674(79)90108-9. [DOI] [PubMed] [Google Scholar]
  12. Robinson S. D., Silberstein G. B., Roberts A. B., Flanders K. C., Daniel C. W. Regulated expression and growth inhibitory effects of transforming growth factor-beta isoforms in mouse mammary gland development. Development. 1991 Nov;113(3):867–878. doi: 10.1242/dev.113.3.867. [DOI] [PubMed] [Google Scholar]
  13. Ruoslahti E., Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell. 1991 Mar 8;64(5):867–869. doi: 10.1016/0092-8674(91)90308-l. [DOI] [PubMed] [Google Scholar]
  14. Sartoris S., Cohen E. B., Lee J. S. A rapid and improved method for generating cDNA libraries in plasmid and phage lambda vectors. Gene. 1987;56(2-3):301–307. doi: 10.1016/0378-1119(87)90148-x. [DOI] [PubMed] [Google Scholar]
  15. Silberstein G. B., Strickland P., Coleman S., Daniel C. W. Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland. J Cell Biol. 1990 Jun;110(6):2209–2219. doi: 10.1083/jcb.110.6.2209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Snedeker S. M., Brown C. F., DiAugustine R. P. Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):276–280. doi: 10.1073/pnas.88.1.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Streuli C. H., Bailey N., Bissell M. J. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol. 1991 Dec;115(5):1383–1395. doi: 10.1083/jcb.115.5.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Talhouk R. S., Chin J. R., Unemori E. N., Werb Z., Bissell M. J. Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture. Development. 1991 Jun;112(2):439–449. doi: 10.1242/dev.112.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Topper Y. J., Freeman C. S. Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev. 1980 Oct;60(4):1049–1106. doi: 10.1152/physrev.1980.60.4.1049. [DOI] [PubMed] [Google Scholar]
  20. Vallee B. L., Auld D. S. Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry. 1990 Jun 19;29(24):5647–5659. doi: 10.1021/bi00476a001. [DOI] [PubMed] [Google Scholar]
  21. Walker N. I., Bennett R. E., Kerr J. F. Cell death by apoptosis during involution of the lactating breast in mice and rats. Am J Anat. 1989 May;185(1):19–32. doi: 10.1002/aja.1001850104. [DOI] [PubMed] [Google Scholar]
  22. Wicha M. S., Liotta L. A., Vonderhaar B. K., Kidwell W. R. Effects of inhibition of basement membrane collagen deposition on rat mammary gland development. Dev Biol. 1980 Dec;80(2):253–256. doi: 10.1016/0012-1606(80)90402-9. [DOI] [PubMed] [Google Scholar]
  23. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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