This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hovey, R. C. Articles by Vonderhaar, B. K. Search for Related Content PubMed PubMed Citation Articles by Hovey, R. C. Articles by Vonderhaar, B. K.

Transcriptional Regulation of Vascular Endothelial Growth Factor Expression in Epithelial and Stromal Cells during Mouse Mammary Gland Development

Laboratory of Tumor Immunology and Biology (R.C.H., A.S.G., B.K.V.) National Cancer Institute and Laboratory of Immunology (J.B.) National Eye Institute National Institutes of Health Bethesda, Maryland 20892

Accompanying changes in the development and function of the mammary gland is the establishment of a vascular network of critical importance for lactogenesis and tumorigenesis. A potent angiogenic and permeability factor that regulates vascular development in association with epithelial-stromal interactions is vascular endothelial growth factor (VEGF). Analysis of VEGF transcription by RT-PCR revealed mRNA for all three VEGF isoforms (VEGF_{120, 164, 188}) within the mammary gland of nulliparous females. During pregnancy the level of VEGF₁₈₈ declined and became undetectable during lactation in association with the increased abundance of VEGF₁₂₀ and VEGF₁₆₄ mRNAs. All three isoforms were expressed at consistent levels within the cleared mammary fat pad throughout development. Furthermore, the presence of VEGF₁₈₈ mRNA in omental adipose tissue at various stages established that VEGF₁₈₈ is expressed specifically in adipose tissue within the mammary gland. Using 3T3-L1 preadipocytes it was demonstrated that VEGF₁₈₈ mRNA transcription occurs as a late event during lipogenesis distinct from earlier induction of VEGF₁₂₀ and VEGF₁₆₄ mRNA during differentiation. In contrast, HC11 mammary epithelial cells only expressed mRNA for VEGF₁₂₀ and VEGF₁₆₄. Localization of VEGF mRNA and protein revealed that VEGF is expressed in stromal cells of the mammary gland in nulliparous females and then undergoes a transition to epithelial expression during lactation. By contrast, mRNA for the VEGF receptors, Flk-1 and Flt-1, localized to stromal cells within the mammary fat pad during virgin and gestational development and was expressed in the interstitial tissue basal to epithelial cells during lactation. Taken together, these results support the conclusion that VEGF is differentially transcribed by specific cell types within the mammary gland, and that under hormonal regulation it functions in an autocrine/paracrine manner.

This article has been cited by other articles:

				S. Tetzlaff, E. Murani, K. Schellander, S. Ponsuksili, and K. Wimmers Differential expression of growth factors and their receptors indicates their involvement in the inverted teat defect in pigs J Anim Sci, November 1, 2009; 87(11): 3451 - 3457. [Abstract] [Full Text] [PDF]

				H. Rossiter, C. Barresi, M. Ghannadan, F. Gruber, M. Mildner, D. Fodinger, and E. Tschachler Inactivation of VEGF in mammary gland epithelium severely compromises mammary gland development and function FASEB J, December 1, 2007; 21(14): 3994 - 4004. [Abstract] [Full Text] [PDF]

				B. E. Dallard, V. Ruffino, S. Heffel, and L. F. Calvinho Effect of a Biological Response Modifier on Expression of Growth Factors and Cellular Proliferation at Drying Off J Dairy Sci, May 1, 2007; 90(5): 2229 - 2240. [Abstract] [Full Text] [PDF]

				E. Ueda, U. Ozerdem, Y.-H. Chen, M. Yao, K. T. Huang, H. Sun, M. Martins-Green, P. Bartolini, and A. M Walker A molecular mimic demonstrates that phosphorylated human prolactin is a potent anti-angiogenic hormone. Endocr. Relat. Cancer, March 1, 2006; 13(1): 95 - 111. [Abstract] [Full Text] [PDF]

				S. Chandrasekharan, N. A. Foley, L. Jania, P. Clark, L. P. Audoly, and B. H. Koller Coupling of COX-1 to mPGES1 for prostaglandin E2 biosynthesis in the murine mammary gland J. Lipid Res., December 1, 2005; 46(12): 2636 - 2648. [Abstract] [Full Text] [PDF]

				M. Tesone, R. L. Stouffer, S. M. Borman, J. D. Hennebold, and T. A. Molskness Vascular Endothelial Growth Factor (VEGF) Production by the Monkey Corpus Luteum During the Menstrual Cycle: Isoform-Selective Messenger RNA Expression In Vivo and Hypoxia-Regulated Protein Secretion In Vitro Biol Reprod, November 1, 2005; 73(5): 927 - 934. [Abstract] [Full Text] [PDF]

				K. Nakagawa, Y. Sasaki, S. Kato, N. Kubodera, and T. Okano 22-Oxa-1{alpha},25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer Carcinogenesis, June 1, 2005; 26(6): 1044 - 1054. [Abstract] [Full Text] [PDF]

				K. Nakagawa, A. Kawaura, S. Kato, E. Takeda, and T. Okano 1{alpha},25-Dihydroxyvitamin D3 is a preventive factor in the metastasis of lung cancer Carcinogenesis, February 1, 2005; 26(2): 429 - 440. [Abstract] [Full Text] [PDF]

				J. R. Beckley, B. U. Pauli, and R. C. Elble Re-expression of Detachment-inducible Chloride Channel mCLCA5 Suppresses Growth of Metastatic Breast Cancer Cells J. Biol. Chem., October 1, 2004; 279(40): 41634 - 41641. [Abstract] [Full Text] [PDF]

				L. Wang, J. H. Kwak, S. I. Kim, Y. He, and M. E. Choi Transforming Growth Factor-{beta}1 Stimulates Vascular Endothelial Growth Factor 164 via Mitogen-activated Protein Kinase Kinase 3-p38{alpha} and p38{delta} Mitogen-activated Protein Kinase-dependent Pathway in Murine Mesangial Cells J. Biol. Chem., August 6, 2004; 279(32): 33213 - 33219. [Abstract] [Full Text] [PDF]

				S.-H. Chang, C. H. Liu, R. Conway, D. K. Han, K. Nithipatikom, O. C. Trifan, T. F. Lane, and T. Hla From the Cover: Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression PNAS, January 13, 2004; 101(2): 591 - 596. [Abstract] [Full Text] [PDF]

				P.D.S. Telles, C.T. Hanks, M.A.A.M. Machado, and J.E. Nor Lipoteichoic Acid Up-regulates VEGF Expression in Macrophages and Pulp Cells Journal of Dental Research, June 1, 2003; 82(6): 466 - 470. [Abstract] [Full Text] [PDF]

				C. Mallet, O. Feraud, G. Ouengue-Mbele, I. Gaillard, N. Sappay, D. Vittet, and I. Vilgrain Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E156 - E167. [Abstract] [Full Text] [PDF]

				P. A. Masso-Welch, D. Zangani, C. Ip, M. M. Vaughan, S. Shoemaker, R. A. Ramirez, and M. M. Ip Inhibition of Angiogenesis by the Cancer Chemopreventive Agent Conjugated Linoleic Acid Cancer Res., August 1, 2002; 62(15): 4383 - 4389. [Abstract] [Full Text] [PDF]