Insulin‐like Growth Factor‐I (IGF‐I) Receptors in Breast Cancer

Pezzino, V.; Papa, Vincenzo; Milazzo, Giovanni; Gliozzo, Biancamaria; Russo, P.; Scalia, Pierluigi

doi:10.1111/j.1749-6632.1996.tb16236.x

Cited by 44 publications

(25 citation statements)

References 27 publications

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“…Thus, one consequence of IGF-IR overexpression in breast cancer could be increased growth and survival of the primary tumor but reduced cell metastasis. This hypothesis is consistent with the observation that the IGF-IR is a good prognostic indicator for breast cancer, as tumors with good prognosis express much higher levels of the IGF-IR than tumors with bad prognosis (1,30,31). Notably, an independent study has shown that in breast tumors, E-cad and ZO-1 are co-expressed and are markers of a more differentiated phenotype (17).…”

Section: Figsupporting

confidence: 87%

IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1

Mauro¹,

Bartucci²,

Morelli³

et al. 2001

Journal of Biological Chemistry

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Hyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes to primary breast cancer development, but the role of the IGF-IR in tumor metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular connections mediated by the major epithelial adhesion protein, E-cadherin (E-cad). We found that IGF-IR overexpression markedly stimulated aggregation in E-cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231 cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells, cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell adhesion of MCF-7 cells was not related to altered expression of E-cad or ␣-, ␤-, or ␥-catenins but coincided with the up-regulation of another element of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1 associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided with an increased IGF-IR/␣-catenin/ZO-1-binding and improved ZO-1/actin association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1 RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell-cell adhesion is overexpression of ZO-1 and the resulting stronger connections between the E-cad complex and the actin cytoskeleton. We hypothesize that in E-cad-positive cells, the IGF-IR may produce antimetastatic effects.

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Section: Figsupporting

confidence: 87%

IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1

Mauro¹,

Bartucci²,

Morelli³

et al. 2001

Journal of Biological Chemistry

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“…Studies have reported that there is a highly significant correlation between a high IGF-IR expression and better prognosis. 31,32 However, several small series studies showed an association with a shorter disease-free survival when the tumors were estrogen receptor-negative and IGF-IRpositive; in addition, these studies indicated that high IGF-IR levels correlated with resistance to radiotherapy. 33,34 The MDA-MB-435s human breast cancer cell line was used in these studies because loss of the estrogen receptor often indicates a poorer prognosis for the patient.…”

Section: Discussionmentioning

confidence: 99%

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

Chernicky

Tan

et al. 2000

Cancer Gene Ther

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The type I insulin-like growth factor receptor (IGF-IR) plays an important role in the growth and transformation of breast cancer cells. In this study, we investigated the effects of treatment with an antisense IGF-IR construct on cells from the highly metastatic estrogen receptor-negative human breast cancer cell line MDA-MB-435s. The cells carrying the antisense IGF-IR had a markedly reduced expression of IGF-IR, had a significant decrease in cell proliferation, and lost the ability to form colonies in soft agar. There was a delay in tumor formation and a dramatic reduction in tumor size when cells carrying the antisense IGF-IR were injected into either nude or severe combined immunodeficient (scid) beige mice. We have also provided data that show that the scid beige mouse is a more suitable model for studying metastasis of the MDA-MB-435s cells. All of the scid beige mice injected with cells carrying the control construct had metastasis to the lungs, whereas lungs from the nude mice had no apparent metastatic sites after 11 weeks. When cells carrying antisense IGF-IR were injected subcutaneously in scid beige mice, the animals had a significant increase in survival compared with mice injected with cells carrying the control construct. Taken together, these results indicate that the IGF-IR can play a critical role in the progression of breast cancer. Our studies provide a basis for the development of future treatment strategies targeting the IGF-IR in metastatic breast cancer. Cancer Gene Therapy (2000) 7, 384 -395

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“…IGF-IR levels have been found to be elevated in primary tumors compared with benign tumors or normal breast epithelium (Milazzo et al 1992, Pezzino et al 1996 and IGF-IR expression correlates to ER status (Peyrat et al 1988). The 200 www.endocrinology.org mechanism by which this occurs is not understood but it is not due to IGF-IR gene amplification (Berns et al 1992).…”

Section: Igf Receptorsmentioning

confidence: 99%

The IGF system and breast cancer.

Sachdev¹,

Yee²

2001

Endocrine-Related Cancer

287

253

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The IGF system components have been implicated in breast cancer progression. IGF-I and IGF-II are mitogenic and anti-apoptotic peptides that influence the proliferation of various cell types including normal and transformed breast epithelial cells. The IGF system is a key growth regulatory pathway in breast cancer. As various components of the IGF system have been directly or indirectly implicated in breast cancer, it is essential to gain a better understanding of these in order to develop more specific therapeutic strategies for treating breast cancer.

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Insulin‐like Growth Factor‐I (IGF‐I) Receptors in Breast Cancer

Cited by 44 publications

References 27 publications

IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1

IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1

Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

The IGF system and breast cancer.

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