The IGF-I receptor in cell growth, transformation and apoptosis

Baserga, Renato; Hongo, Atsushi; Rubini, Michele; Prisco, Marco di; Valentinis, Barbara

doi:10.1016/s0304-419x(97)00007-3

Cited by 313 publications

(336 citation statements)

References 150 publications

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“…Furthermore, synergy with antisense ODN was achieved with very low concentrations of MMC agent (Fig 7), thus minimizing their toxicity and maximizing their therapeutic application in vitro. Studies on the function of IGF-1R follow one topic: IGF-1R plays crucial role in the mechanism of anti-apoptosis [8], [9]. In this study, knockdown of IGF-1R by antisense ODN can significantly enhance apoptotic sensitivity of T24 cells to MMC, which was consistent with this hypothesis about the involvement of IGF-1R in apoptosis.…”

Section: Discussionsupporting

confidence: 89%

“…It should be pointed out: (1) Targeting the IGF-1R is more efficient than targeting its ligands because targeting one ligand leaves other one free to activate the IGF-1R [8]. (2) The bladder is particularly amenable to such experimental treatment, because its special anatomic structure and localized therapy is possible by intravascular administration, thus minimizing side effects [20].…”

Section: Discussionmentioning

confidence: 99%

“…It plays an important role in both normal and abnormal growth, particularly in anchorage independent growth. Impairment of its function caused apoptosis of some kinds of cancer cells and inhibition of tumor growth in experimental animals [8,9]. Some investigators also provided evidences that IGF-1R signaling might be implicated in the mechanism of drug resistance in human breast cancer and multiple myeloma [5,10,11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Sun

Shu

2001

Cell Res

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A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Sun

Shu

2001

Cell Res

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“…The insulin-like growth factor 1 receptor (IGF-1R), a tetrameric receptor tyrosine kinase (RTK), is important for transformation, proliferation of malignant cells (Baserga, 1995;Baserga et al, 1997;Adams et al, 2000;LeRoith and Roberts, 2003;Larsson et al, 2005), crucial for preventing apoptosis, maintaining malignant phenotype and for resistance to chemotherapy (Baserga, 1995(Baserga, , 2000Yu and Rohan, 2000;Samani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and β-arrestin1

Vasilcanu

Rosengren

et al. 2007

Oncogene

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The insulin-like growth factor 1 receptor (IGF-1R) is crucial for growth and survival of malignant cells. Experience in targeting IGF-1R in cancer models has shown that strategies promoting downregulation of the receptor are much more efficient in inducing apoptosis than those inhibiting the IGF-1R activity. Recently, we found that the cyclolignan picropodophyllin (PPP) inhibits phosphorylation of IGF-1R and activation of downstream signaling without interfering with the highly homologous insulin receptor (IR). Furthermore, PPP treatment caused strong regression of tumor grafts and prolonged survival of animals with systemic tumor disease. Here we demonstrate that PPP also downregulates the IGF-1R, whereas the IR and several other receptors were not affected. PPP-induced IGF-1R downregulation required expression of the MDM2 E3 ligase, which recently was found to ubiquitinate and cause degradation of the IGF-1R. In addition knockdown of barrestin1, the adaptor molecule known to bridges MDM2 and IGF-1R, prevented downregulation of the receptor and significantly decreased PPP-induced cell death. All together these data suggest that PPP downregulates IGF-1R by interfering with the action of b-arrestin1/MDM2 as well as the achieved receptor downregulation contributes to the apoptotic effect of PPP.

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“…The IGF-1R promoter exhibits a high basal transcriptional activity, and is under physiological control of nutritional factors (Olchovsky et al, 1993), hormonal stimulation (Clarke et al, 1997) and the developmental stage (Bondy et al, 1992). Its expression is altered in certain diseases, including cancer (LeRoith et al, 1995a;Baserga et al, 1997).…”

Section: Interactions Between Igf-1r and Oncogenesmentioning

confidence: 99%

Role of insulin-like growth factor 1 receptor signalling in cancer

2005

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The insulin-like growth factor (IGF-1) signalling is highly implicated in cancer. In this signalling the IGF-1 receptor (IGF-1R) is unquestionable, the predominating single factor. IGF-1R is crucial for tumour transformation and survival of malignant cell, but is only partially involved in normal cell growth. This is in part due to the interactions with oncogenes. Recent findings suggest a close interplay with the p53/MDM2 pathway. Disturbances in components in the p53/MDM2/IGF-1R network may cause IGF-1R upregulation and growth advantage for the cancer cell. Targeting of IGF-1R is more and more seen as a promising option for future cancer therapy. Single chain antibodies and small molecules with selective effects on IGF-1R dependent malignant growth are of particular interest. Forthcoming clinical trials are welcome and will indeed be the only way to evaluate the impact of IGF-1R targeting in human cancer.

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The IGF-I receptor in cell growth, transformation and apoptosis

Cited by 313 publications

References 150 publications

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Picropodophyllin induces downregulation of the insulin-like growth factor 1 receptor: potential mechanistic involvement of Mdm2 and β-arrestin1

Role of insulin-like growth factor 1 receptor signalling in cancer

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