Comparison of the Mitogenic Potency of Regular Human Insulin and its Analogue Glargine in Normal and Transformed Human Breast Epithelial Cells

Staiger, K.; Hennige, Anita M.; Staiger, H; Häring, HU; Kellerer, Monika

doi:10.1055/s-2007-957352

Cited by 50 publications

(53 citation statements)

References 8 publications

(18 reference statements)

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“…These results are at variance with those of Staiger et al (2007) and Liefvendahl & Arnqvist (2008) who did not see this effect with their approach.…”

Section: Discussioncontrasting

confidence: 56%

“…Thus, the mammary gland may represent a sensitive target for growth stimulation by insulin analogs. Reports on the proliferative effect of insulin analogs on mammary epithelial cells in vitro (Slieker et al 1997, Gammeltoft et al 1999, Staiger et al 2007, Liefvendahl & Arnqvist 2008 showed varying results regarding the mitogenic potency of the compounds. However, results from different studies are difficult to compare because data have been obtained under different experimental conditions and evaluated by different procedures.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines

Shukla¹,

Grisouard²,

Ehemann³

et al. 2009

Endocrine-Related Cancer

120

125

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Insulin and insulin analogs stimulate proliferation of human mammary epithelial cells. We identified and analyzed the signaling pathways related to cell proliferation induced by regular insulin and by four insulin analogs presently approved for therapeutical use. Benign and malignant mammary cell lines showing different insulin receptor (IR) and IGF-I receptor (IGF-IR) expression patterns were studied. Cell proliferation was studied by crystal violet staining (BrdU-FACS analysis). Activation of insulin and IGF signaling pathways was studied by analysis of the phosphorylation status of IGF-IR and of key signaling proteins of the phosphoinositide 3-kinase (PI3K)/Akt and MAP kinase pathways, by the use of specific PI3K and MAP kinase inhibitors, and by silencing of IR and IGF-IR. Lantus stimulated the growth of MCF7 cells, which show high IGF-IR/IR ratio, significantly at 0.3 nmol/l, while regular insulin (Actrapid and bovine insulin) and other insulin analogs (Novorapid, Humalog, and Levemir) stimulated cell growth at 1.5-15 nmol/l concentrations. No difference between Lantus and the other insulin analogs was observed regarding growth stimulation of MCF10A cells showing low IGF-IR/IR ratio. Growth stimulation of MCF7 cells by Lantus was mainly due to strong activation of the IGF-IR and the MAP kinase pathway. Regular insulin and other insulin analogs tested activated mainly the IR and the PI3K/Akt pathway. We conclude that unlike regular insulin and other insulin analogs, Lantus strongly activates the IGF-IR and the MAP kinase pathway in MCF7 cells and is a strong mitogen for cells characterized by a high-IGF-IR/IR ratio.

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“…These results are at variance with those of Staiger et al (2007) and Liefvendahl & Arnqvist (2008) who did not see this effect with their approach.…”

Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines

Shukla¹,

Grisouard²,

Ehemann³

et al. 2009

Endocrine-Related Cancer

120

125

View full text Add to dashboard Cite

show abstract

“…Of interest, a recent study showed that both regular insulin and glargine at doses of 50-100 nM significantly enhanced 3 [H]thymidine uptake and MTT-assayed proliferation of normal human breast epithelial cells (MCF-10) and MCF-7 breast cancer cells. No differences, however, were seen in this study between regular insulin and analogue [27].…”

Section: Discussioncontrasting

confidence: 48%

Insulin analogues display IGF‐I‐like mitogenic and anti‐apoptotic activities in cultured cancer cells

Weinstein

Simon

Yehezkel

et al. 2009

Diabetes Metabolism Res

162

141

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“…Conversely, insulin glargine and insulin detemir were both able to stimulate the growth of mouse fi broblasts to greater extent than native insulin in the presence of either IR-A, IR-B or IGF-1R; IGF-1 stimulated proliferation only in cells containing IGF-1R [34] . However, the fi ndings of Shukla et al are inconsistent with those reported by Staiger et al [38] , who compared the mitogenic potency ( 3 H-thymidine incorporation) of insulin glargine, human insulin and a negative control in MCF-7 and MCF-10 cells. Although MCF-10 cells showed enhanced 3 H-thymidine incorporation with insulin glargine, this was not signifi cantly diff erent from that elicited by human insulin.…”

Section: In Vitro Studies Of Insulin Glarginecontrasting

confidence: 56%

“…Other studies have confi rmed this observation using cell-based assays [14,33,34,38,41,44] . However, these studies have also demonstrated that the relative affi nity of insulin analogues for IGF-1R is still much lower than that of the natural ligand IGF-1.…”

Section: Discussion ▼mentioning

confidence: 85%

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2011

Horm Metab Res

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Comparison of the Mitogenic Potency of Regular Human Insulin and its Analogue Glargine in Normal and Transformed Human Breast Epithelial Cells

Cited by 50 publications

References 8 publications

Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines

Analysis of signaling pathways related to cell proliferation stimulated by insulin analogs in human mammary epithelial cell lines

Insulin analogues display IGF‐I‐like mitogenic and anti‐apoptotic activities in cultured cancer cells

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