This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Johnston, P. G. Articles by Allegra, C. J. Search for Related Content PubMed PubMed Citation Articles by Johnston, P. G. Articles by Allegra, C. J.

Identification of a Protein Factor Secreted by 3T3-L1 Preadipocytes Inhibitory for the Human MCF-7 Breast Cancer Cell Line

National Cancer Institute-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda 20889 [P. G. J., D. V., C. J. A.], and Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, NIH, Bethesda 20892 [C. M. R.], Maryland

¹ To whom requests for reprints should be addressed, at NCI-Navy Medical Oncology Branch, National Cancer Institute, NIH, Naval Hospital Bethesda, Building 8, Room 5101, Bethesda, MD 20889.

The 3T3-L1 cell line is a preadipocyte cell line derived from the Swiss 3T3 mouse fibroblast cell line. We have compared the effect of 3T3-L1 conditioned medium (3T3-L1 CM) and Swiss 3T3 conditioned medium (3T3 CM) on the growth of normal mouse mammary cells (NMMG) and the human MCF-7 breast carcinoma cell line. 3T3 CM increased the growth of both NMMG and MCF-7 cells by 19 ± 2% (SD) and 24 ± 3%, respectively, and increased thymidine incorporation by 74 ± 4% and 104 ± 8%, respectively. Conditioned medium from 3T3-L1 cells stimulated the growth of NMMG cells by 64 ± 2%; in contrast, 3T3-L1 CM inhibited the growth of MCF-7 cells by 36 ± 1%. In parallel with these growth studies, thymidine incorporation increased by 20 ± 4% in NMMG cells and decreased by 72 ± 5% in the MCF-7 cells. Moreover, a similar effect was also noted in NCI H630 colon cancer cells, where 3T3-L1 CM produced a 58 ± 4% decrease in growth and a 82 ± 6% decrease in thymidine incorporation. Heating the 3T3-L1 CM at 100°C for 30 min destroyed all inhibitory activity. Several known inhibitory growth factors (fibroblast growth factor, 20 ng/ml; interleukin 6, 1000 units/ml; tumor necrosis factor , 15 ng/ml; transforming growth factor β, 1 ng/ml) were tested for activity in the MCF-7 cells. Tumor necrosis factor and transforming growth factor β produced a 97% and 67% inhibition of thymidine uptake, respectively, whereas interleukin 6 and fibroblast growth factor had no effect. Neither transforming growth factor β nor tumor necrosis factor a activity was detectable in 3T3-L1 CM using an enzyme-linked immunosorbent assay. High-performance liquid chromatography fractionation of the 3T3-L1 CM revealed that the inhibitory activity eluted at a molecular weight of 67,000; moreover, silver staining of these eluates on a denaturing polyacrylamide gel revealed that M_r 69,000 peptide was the predominant protein band in the inhibitory fractions. Thus 3T3-L1 CM stimulates the growth of normal breast epithelial cells and inhibits the growth of MCF-7 breast cancer cells. This inhibitory activity appears to be due to a protein secreted by 3T3-L1 preadipocytes.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/16/92. Accepted 10/ 7/92.

This article has been cited by other articles:

				A. Stuedal, H. Ma, L. Bernstein, M. C. Pike, and G. Ursin Does Breast Size Modify the Association between Mammographic Density and Breast Cancer Risk? Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 621 - 627. [Abstract] [Full Text] [PDF]

				M. E. Trujillo and P. E. Scherer Adipose Tissue-Derived Factors: Impact on Health and Disease Endocr. Rev., December 1, 2006; 27(7): 762 - 778. [Abstract] [Full Text] [PDF]

				A M Lorincz and S Sukumar Molecular links between obesity and breast cancer. Endocr. Relat. Cancer, June 1, 2006; 13(2): 279 - 292. [Abstract] [Full Text] [PDF]

				J. E. Celis, J. M. A. Moreira, T. Cabezon, P. Gromov, E. Friis, F. Rank, and I. Gromova Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients: Toward Dissecting The Molecular Circuitry of Epithelial-Adipocyte Stromal Cell Interactions Mol. Cell. Proteomics, April 1, 2005; 4(4): 492 - 522. [Abstract] [Full Text] [PDF]

				B. Xie, S.W. Tsao, and Y.C. Wong Sex hormone-induced mammary carcinogenesis in female Noble rats: the role of androgens Carcinogenesis, August 1, 1999; 20(8): 1597 - 1606. [Abstract] [Full Text] [PDF]