Insulin-like growth factors and cancer

Macaulay, Valentine M.

doi:10.1038/bjc.1992.65

Cited by 496 publications

(276 citation statements)

References 120 publications

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“…There is increasing evidence that the growth hormone-IGF-I axis plays a role in carcinogenesis in the breast (Pollak, 1998;Ruan et al, 1992) and transgenic mice that over-express IGF-I or growth hormone have an increased incidence of mammary cancer (Tornell et al, 1992;Macaulay, 1992;Ruan et al, 1992;Yee, 1998). The administration of growth hormone to ageing female monkeys induced hyperplasia of the mammary epithelium, with a striking increase in the number and cellularity of lobules, and an increase in the mitotic labelling index (Ng et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

The association of breast mitogens with mammographic densities

et al. 2002

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Radiologically dense breast tissue (mammographic density) is strongly associated with risk of breast cancer, but the biological basis for this association is unknown. In this study we have examined the association of circulating levels of hormones and growth factors with mammographic density. A total of 382 subjects, 193 premenopausal and 189 postmenopausal, without previous breast cancer or current hormone use, were selected in each of five categories of breast density from mammography units. Risk factor information, anthropometric measures, and blood samples were obtained, and oestradiol, progesterone, sex hormone binding globulin, growth hormone, insulin-like growth factor-I and its principal binding protein, and prolactin measured. Mammograms were digitised and measured using a computer-assisted method. After adjustment for other risk factors, we found in premenopausal women that serum insulin-like growth factor-I levels, and in postmenopausal women, serum levels of prolactin, were both significantly and positively associated with per cent density. Total oestradiol and progesterone levels were unrelated to per cent density in both groups. In postmenopausal women, free oestradiol (negatively), and sex hormone binding globulin (positively), were significantly related to per cent density. These data show an association between blood levels of breast mitogens and mammographic density, and suggest a biological basis for the associated risk of breast cancer.

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Section: Discussionmentioning

confidence: 99%

The association of breast mitogens with mammographic densities

et al. 2002

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“…1,2 The mitogenic and antiapoptotic activities of IGFs are regulated by six IGF-binding proteins (IGFBPs), namely IGFBP1 to IGFBP6. IGFBPs either inhibit or enhance the action of IGFs, depending on cell type and physiologic/ pathologic status, resulting in either suppression or stimulation of cell proliferation.…”

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confidence: 99%

“…IGFBPs either inhibit or enhance the action of IGFs, depending on cell type and physiologic/ pathologic status, resulting in either suppression or stimulation of cell proliferation. 1,2 Among the six IGFBPs, IGFBP2 is overexpressed in many malignancies such as prostatic cancer, human glioma, etc. 3 Overexpression of IGFBP2 in these tumors is often associated with increased aggressiveness of the tumor.…”

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confidence: 99%

Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types

et al. 2006

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The family of insulin-like growth factor-binding proteins (IGFBPs) comprises six members, which bind and regulate the functions of insulin-like growth factors. Overexpression of IGFBP2 and IGFBP5 contributes to the invasiveness and progression of several human cancers, but their role and clinical significance in ovarian cancer has not been investigated in detail. We examined IGFBP2 and IGFBP5 expression levels using two tissue microarrays, one containing six normal surface epithelium, six benign serous cysts, 10 serous borderline tumors, eight low-grade, and 20 high-grade serous carcinomas. The other comprising 441 ovarian cancers of different histologic types linked to a clinicopathologic database. Each tumor was sampled in duplicate with a 1.0-mm punch core needle. Immunohistochemical staining was performed using antibodies against IGFBP2 or IGFBP5. The staining intensity was scored semiquantitatively as negative (0), weak (1-10%), moderate (10-50%), or strong (50-100%) using computerized image analysis. Statistical analyses used Fisher's exact test and Kaplan-Meier method. IGFBP2 and IGFBP5 were overexpressed in high-grade serous carcinomas compared to normal surface epithelium, benign serous cysts, serous borderline tumors, or low-grade serous carcinoma. They were differentially expressed in different types of ovarian carcinomas, being more often expressed at high levels in high-grade serous carcinoma, malignant mixed mullerian tumors and undifferentiated carcinoma, and more often expressed at low levels or not at all in clear cell and mucinous carcinomas. We concluded that IGFBP2 and IGFBP5 might play a role in the development of high-grade ovarian serous carcinoma, but not in mucinous or clear cell ovarian carcinomas.

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“…1 Insulin-like growth factor 1 (IGF-1) has been shown to be an important mitogenic and antiapoptotic peptide in many tumours. 2 It affects the proliferation of normal and malignant cells through both endocrine and paracrine actions. Studies have shown that human prostate cancer cell lines demonstrate an increase in functional IGF-1.…”

Section: Introductionmentioning

confidence: 99%

“…For example, a family member of a patient with prostate cancer found to have higher than usual serum IGF-1 may be advised to start therapy designed to reduce the levels. 2,4,17,18 Furthermore, plasma IGFBP-3 levels are reported to be highest in healthy subjects, followed by patients with localized prostate cancer, while levels are lowest in those with skeletal metastases. 8,15 Most of the previous epidemiological studies on IGF1 and IGFBP3 (except that by Chokkalingam et al 7 conducted on the Chinese) were in Caucasians with known high risk for prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Putative role of serum insulin-like growth factor–1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels in the development of prostate cancer in Arab men

Kehinde

Akanji

Mojiminiyi

et al. 2005

Prostate Cancer Prostatic Dis

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Introduction: The incidence of clinical prostate cancer in the Arab population is among the lowest in the world. High serum IGF-1 level has been implicated as a possible risk factor for the development of prostate cancer in Caucasians. The purpose of this study was to determine serum IGF-1 and IGFBP-3 levels in healthy Arab men and in Arab men with newly diagnosed benign prostatic hyperplasia (BPH) and prostate cancer, and to compare these values with values reported in Caucasians. Patients and Methods: Subjects were recruited in two groups: (a) indigenous, healthy Arab men aged 15-90 y (n ¼ 383); (b) Arab men with newly diagnosed prostate cancer (n ¼ 30) or BPH (n ¼ 40). Blood was obtained from fasting patients and volunteers, between 8:00 a.m. and 12:00 noon. The serum concentrations of IGF-1 and IGFBP-3 were determined using Immunoradiometric assay (IRMA) kits. Results: As in Caucasians, serum IGF-1 and IGFBP-3 levels declined with age in Arab men. The mean7s.d. of serum IGF-1 levels in healthy Arab men in the age group 15-20, 51-60, 61-70 y were lower (376.27153.2, 134.97105.7 and 89.6748.4 ng/ml, respectively), compared to values reported for similarly aged Caucasians. Arab men with newly diagnosed prostate cancer had significantly higher serum IGF-1 level (Po0.01) and lower IGFBP-3 levels (Po0.01) compared to age-matched Arabs without the disease. Conclusions: Arab men have lower serum IGF-1 levels compared to Caucasians and this may be an important factor in the explanation of the low incidence of prostate cancer in the Arab population.

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Insulin-like growth factors and cancer

Cited by 496 publications

References 120 publications

The association of breast mitogens with mammographic densities

The association of breast mitogens with mammographic densities

Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types

Putative role of serum insulin-like growth factor–1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels in the development of prostate cancer in Arab men

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