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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mammary gland biology and neoplasia 2 (1997), S. 143-151 
    ISSN: 1573-7039
    Keywords: Mammary gland ; autocrine growth ; growth factors ; neoplastic transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Normal mammary gland development is the result of complex interactions between a number of hormones and growth factors. Normal and malignant human mammary epithelial cells are able to synthesize and to respond to various different, locally acting growth factors and growth inhibitors. Among these, the EGF-related peptides play an important role in regulating the proliferation and differentiation of human mammary epithelial cells. EGF4 and TGFα are able to stimulate the lobulo-alveolar development of the mammary gland in vivo as well they are involved in the pathogenesis of human breast cancer. Experimental evidence suggests that estrogen-induced proliferation of breast carcinoma cells is mediated in part by EGF-related growth factors. It has also been demonstrated that activation of certain cellular protooncogenes such as c-Ha-ras in human mammary epithelial cells results in cellular transformation and in an increased production of several EGF-related growth factors such as TGFα and amphiregulin. Coexpression of both EGF-related peptides and their own receptors frequently occurs in human breast carcinomas and in human breast cancer cell lines, suggesting that an autocrine pathway of uncontrolled cell growth sustains neoplastic transformation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 33 (1995), S. 103-114 
    ISSN: 1573-7217
    Keywords: amphiregulin ; breast tumors ; EGF receptor ; oncogenes ; steroid hormones ; transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Amphiregulin (AR) is an epidermal growth factor (EGF)-related peptide that operates exclusively through the EGF receptor and that can bind to heparin. AR also possesses nuclear localization sequences in the extended NH2-terminal region suggesting an additional intracellular site of action. AR mRNA and protein expression have been detected in primary human mammary epithelial cell strains, nontransformed human mammary epithelial cell lines, several human breast cancer cell lines, and primary human breast carcinomas. The frequency and levels of AR protein expression are generally higher in invasive breast carcinomas than in ductal carcinomasin situ or in normal, noninvolved mammary epithelium. In addition, AR can function as an autocrine and/or juxtacrine growth factor in human mammary epithelial cells that have been transformed by an activated c-Ha-ras proto-oncogene or by overexpression of c-erb B-2. AR expression is also enhanced by mammotrophic hormones such as estrogens and other growth factors such as EGF.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: growth factors ; antisense ; receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract MDA-468 human breast cancer cells overexpress the EGFR and exhibit a functional TGFα-EGFR autocrine pathway. Loss of EGFR expression following stable transfection with an antisense EGFR cDNA containing plasmid down-regulates type I cAMP-dependent protein kinase (PKAI) expression with acquisition of cell growth resistance to the PKAI inhibitor 8-Cl-cAMP. These results suggest that PKAI expression and function are controlled by a TGFα-EGFR autocrine pathway in human breast cancer cells overexpressing the EGFR.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; amphiregulin ; heregulin ; cripto-1 ; EGF receptor family
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1) mRNA transcripts was assessed in 60 human primary breast carcinoma. AR and HRG transcripts were expressed respectively in 58% and 25% of the carcinomas as measured by Northern blot analysis. CR-1 mRNA was found in 77% of the carcinomas using Reverse Transcriptase-PCR analysis. Coexpression of two or three of these peptides was observed in several specimens. There was no significant association between AR, HRG, and CR-1 expression and nodal status, EGF receptor, or c-erbB-2 protooncogene expression in these tumors. However, a significant association between AR expression and estrogen receptor positivity was observed.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The proto-oncogene c-myc and the oncogene SV40T, both of which have been implicated in the process of cellular immortalization in vitro, have been introduced via amphotropic retroviral expression vectors into the human mammary epithelial cell (HMEC) line 184A1N4 (A1N4). Two stable cell lines were established by growth in selective medium and were found to overexpress either c-myc (A1N4-myc) or SV40T antigen (A1N4-T). Neither the A1N4, A1N4-myc, or A1N4-T cells will grow in soft agar or form tumors in nude mice. However, A1N4-T or A1N4-myc cells, but not the parental A1N4 cells, form colonies in soft agar in response to either epidermal growth factor (EGF), transforming growth factor α (TGFα), or basic fibroblast growth factor (bFGF). Like EGF and TGFα, bFGF is moderately mitogenic for the anchorage-dependent growth (ADG) of all three cell lines. Further, co-cultivation of A1N4-T or A1N4-myc cells with primary diploid mammary fibroblasts can also induce the anchorage-independent growth (AIG) and stimulate the ADG of A1N4-T or A1N4-myc. In addition, conditioned medium obtained from these mammary fibroblasts also stimulated the AIG of the A1N4-T and A1N4-myc cells and was found to contain immunoreactive TGFα and bioactive FGF. The mammary fibroblasts express specific mRNA transcripts for bFGF and acidic FGF (aFGF). These results suggest that growth factors such as TFGα or FGF, which may be derived from the adjacent mammary stroma, might influence in a paracrine manner the phenotypic characteristics of a population of human mammary epithelial cells toward transformation.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 42 (1990), S. 45-57 
    ISSN: 0730-2312
    Keywords: oncogenes ; neoplastic transformation ; transforming growth factor-α ; transforming growth factor-β ; basic fibroblast growth factor ; platelet-derived growth factor ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: The expression of growth factor-specific mRNA transcripts and the presence of biologically active growth factors in the conditioned medium and in the cell extracts from mouse NIH-3T3 cells transformed by different oncogences (Ki-ras, mos, src, fms, fes, met, and trk), by DNA tumor virus (SV40), or by a chemical carcinogen (N-nitrosomethylurea) were studied. In contrast to NIH-3T3 cells or simain virus 40 (SV40)-transformed 3T3 cells, all the other transformed NIH-3T3 cell lines express a 4.5 kb transforming growth factor-α (TGFα)-specific mRNA transcript and secreted immunoreactive and biologically active TGFα ranging from 100 to 225 ng/108 cell/48 h. In addition, in the transformed cell lines that were secreting elevated levels of biologically active TGFα, there was a 75-95% reduction in the total number of epidermal growth factor receptors on these cells. A 2.6 kb TGFβ mRNA transcript and TGFβ protein in the conditioned medium (30-140ng/108 cells/48h) was also detected in those lines expressing TGFα. Basic fibroblast growth factor-like activity (11-50 ng/108 cells) was detected in the cell lysates from NIH-3T3 cells transformed with N-nitrosomethylurea or with trk, where expression of specific 6.9 and 3.9 kb mRNA transcripts for basic fibroblast growth factor could also be found. B chain (c-sis) expression of platelet-derived growth factor was present only in trk-transformed NIH-3T3 cells in which specific c-sis 6.5 and 4.6 kb transcripts were identified. In contrast, platelet-derived growth factor A chain expression of 2.9 and 2.3 kb transcripts was found in ras-, met-, mos-, and fms-transformed NIH-3T3 cells. These results suggest that the expression of different sets of growth factors is controlled in part by structurally distinct groups of transforming genes.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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