Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that transforming growth factor-alpha (TGF-alpha) is a mitogenic autocrine growth factor for human breast cancer cells, responsible for mediating the mitogenic effects of 17 beta-estradiol (E2) in responsive cells. To test this hypothesis we have introduced eukaryotic expression vectors directing the expression of TGF-alpha mRNA into E2-responsive MCF-7 human breast cancer cells. Transfected cells produce levels of TGF-alpha equivalent to or greater than those produced by both E2-stimulated MCF-7 cells and hormone-independent MDA-MB-231 cells. One transfected clone (H8) secretes sufficient TGF-alpha to fully down-regulate EGF-R expression. However, both of the transfected clones that constitutively secrete elevated levels of TGF-alpha (A8 and H8) respond to E2 stimulation in vitro by increasing the rate of cellular proliferation and inducing PGR synthesis. The basal proliferative capacity of H8 and A8 cells is equivalent to that of the parental cells and to cells transfected only with the G418 (neomycin) resistance gene. Furthermore, the TGF-alpha cDNA-transfected clones do not form tumors in ovariectomized athymic nude mice without E2 supplementation. Thus, the precise role of TGF-alpha in mediating either the in vivo or the in vitro mitogenic effects of E2 in MCF-7 human breast cancer cells remains unclear. While TGF-alpha expression may be essential, it is not sufficient alone to induce the fully E2-independent phenotype. Thus, TGF-alpha may function in combination with other E2-induced growth factors to control breast cancer proliferation and tumorigenesis.
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PMID:The effects of a constitutive expression of transforming growth factor-alpha on the growth of MCF-7 human breast cancer cells in vitro and in vivo. 271 Jan 38

The proliferation of human non-small-cell-lung-cancer (NSCLC) cells is regulated by the epidermal-growth-factor-receptor (EGFR)-mediated autocrine loop that interacts with transforming growth factor-alpha (TGF-alpha) of autocrine or paracrine origin. We have shown that EGFR expression is elevated in the brain metastatic variant of human NSCLC cells H226Br, which thereby acquire their increased sensitivity toward exogenous TGF-alpha. To determine detailed cell-phenotype changes as a result of EGFR down-regulation, H226Br cells were transfected with a human EGFR-cDNA construct encompassing an N-terminal fragment (1.8 kb) in anti-sense orientation downstream of the cytomegalovirus (CMV) promoter. The EGFR transcript expressed in the 3'-5' direction is expected to neutralize EGFR mRNA and to reduce protein expression correspondingly. The established cell lines resistant to G418 were shown integrated with the transfected construct and their proliferation rates reduced as compared with the parental cells and with those transfected with vector alone. Down-regulated EGFR expression in cells with the anti-sense construct can be confirmed by Scatchard analysis and suppressed EGFR kinase activity. The restrained-growth phenotype is also demonstrated in the prolonged G2-M phase during the cell cycle, and correlated with impairment of cell proliferation. This finding suggests that EGFR over-expression is critical in maintaining the malignant phenotype of NSCLC cells, thereby providing a valuable biomarker and potential target prevention for lung-cancer-cell proliferation.
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PMID:Transfection of anti-sense complementary DNA of human epidermal-growth-factor receptor attenuates the proliferation of human non-small-cell-lung-cancer cells. 1020 64