If you have or are thinking about doing IGF I would read this...

[boston789]

http://www.mindfully.org/Health/IGF-1-Cancer-BMJ7oct01.htm

Cancer and insulin-like growth factor-I (IGF-1 )
Editorial / British Medical Journal BMJ 2000;321:847-848 7oct00
The milk from cows treated with rBGH (recombinant bovine growth hormone, a genetically engineered hormone by Monsanto that is injected into cows to make them produce more milk), has higher levels of IGF-1. Contrary to the claims of Monsanto, it is not destroyed in the human stomach.

A potential mechanism linking the environment with cancer risk The milk from cows treated with rBGH (recombinant bovine growth hormone, a genetically engineered hormone by Monsanto that is injected into cows to make them produce more milk), has higher levels of IGF-1. Contrary to the claims of Monsanto, it is not destroyed in the human stomach.


Insulin-like growth factor-I acts as an important mediator between growth hormone and growth throughout fetal and childhood development. Its effects and those of the other insulin-like growth factors are modulated by at least six different binding proteins. The role of insulin-like growth factor-I in promoting cancer has been investigated for many years, but recently the quality and quantity of evidence has increased.1 In particular, a number of prospective studies using stored blood collected up to 14 years before the onset of disease have shown associations between insulin-like growth factor-I and prostate cancer, premenopausal breast cancer, and colon cancer.2-4

The risk of cancer is higher among people with raised concentrations of insulin-like growth factor-I, and it is lower among those with high concentrations of insulin-like growth factor binding protein-3 (the main binding protein). The associations are similar when people whose blood samples were taken soon before diagnosis are excluded from analyses, suggesting that the observed relations are not due to the release of the growth factor by preclinical cancers.2-4 The effects are sizeable and stronger than the effects seen in relation to most previously reported risk factors.1 Weaker evidence from case-control studies suggests that the ratio of insulin-like growth factor-I to insulin-like growth factor binding protein-3 may also be related to the risk of childhood leukaemia and lung cancer. 5 6

The increasing direct epidemiological evidence that relates insulin-like growth factor-I to the risk of cancer is consistent with more circumstantial evidence. Acromegaly, in which high concentrations of growth hormone stimulate production of high concentrations of insulin-like growth factor-I, has been associated with an increased risk of colorectal cancer and breast cancer in some studies and less consistently with prostate, thyroid, and haematological malignancies.7 In many studies anthropometric markers of the activity of insulin-like growth factor-I, such as height and leg length, are associated with cancer incidence, particularly with the cancers for which risk increases with rising concentrations of insulin-like growth factor-I.8 While adult height is not strongly associated with concentrations of insulin-like growth factor-I in cross sectional studies, it may be a marker for this growth factor during childhood growth,9 and this may be the period during which it acts to increase the risk of cancer occurring in later life.3 Additionally, animal studies have shown that high overall intake of energy in early postnatal life is associated with an increased cancer risk, and this association has recently been found in humans.10 In animals, calorie restriction reduces the risk of cancer primarily by reducing the circulating concentrations of insulin-like growth factor-I.11

Support for the link between cancer and this growth factor comes from an understanding of the potential mechanisms. Concentrations of insulin-like growth factor-I could be a surrogate for the activity of sex steroid hormones, which in turn influence the risk of cancer. However, associations between insulin-like growth factor-I and cancers dependent on sex hormones are stronger than those between directly measured concentrations of sex hormones and these cancers. Insulin-like growth factor-I may increase cell turnover and the susceptibility of cells to malignant transformation both directly and by modulating the effects of sex steroids. The fact that the risk associated with increased concentrations of insulin-like growth factor-I is greater in people whose DNA is more susceptible to damage induced by mutagens supports this suggestion.6 Alternatively, insulin-like growth factor-I might increase the risk of cancer through its anti-apoptotic activity.1 In this case it prevents the programmed death of cells that have been transformed thus interrupting an important process which retards the development of cancer. Experiments using animal and cell cultures have shown that the anti-apoptotic activity of insulin-like growth factor-I is counterbalanced by the activity of insulin-like growth factor binding protein-3, which may have a direct and independent stimulatory action on apoptosis.

Given the increasing evidence of the risk of cancer, caution should be exercised in the exogenous use of either insulin-like growth factor-I or substances that increase concentrations of it. Despite supposedly being restricted to use only in licensed applications, growth hormone is easily available as an anti-ageing treatment and is surprisingly widely used by athletes and body builders, who also use insulin-like growth factor-I. Those who use these products are unlikely to be aware of their potentially harmful effects.

The final accounting on the balance sheet of growth hormone, insulin-like growth factor-I, and chronic disease is uncertain. The increasing evidence of a risk of cancer may be counterbalanced by a protective effect on the risk of cardiovascular disease. Growth hormone deficiency is associated with an adverse cardiovascular risk profile and increased risk of mortality from cardiovascular disease.12 Low concentrations of insulin-like growth factor-I are also associated with cardiovascular morbidity in the elderly.13 Furthermore, the same studies that have shown a positive association between height and cancer risk suggest that greater height is associated with decreases in cardiovascular and all cause mortality.14

The predictive value of insulin-like growth factor-I may be useful in screening for cancer. For example, the ratio of insulin-like growth factor-I to prostate specific antigen may be a better predictor of the development of prostate cancer than the antigen alone.15 Growth hormone antagonists are being investigated as treatments for some cancers and chemotherapeutic agents are being developed to block the activity of insulin-like growth factor-I or to promote the activity of insulin-like growth factor binding protein-3; these agents may offer additional ways of stimulating apoptosis in malignantly transformed cells. Lastly, better knowledge of the factors that influence overall concentrations of insulin-like growth factor-I may help in devising strategies to prevent cancer at a population level.

Much recent attention has focused on the human genome project and its potential for unravelling the causes of cancer. The genes that have been identified as causing cancer so far account for only a small proportion of major cancers. The rapid and sizeable changes in the incidence of cancer that have been seen during times of economic development coupled with the findings from twin studies - which compare the concordance of cancer risk in identical and non-identical twins to determine the relative influence of genetic and environmental factors - both point to the importance of non-genomic factors.16 The new epidemiological findings about insulin-like growth factor-I provide one potential mechanism through which an array of previously identified environmental risk factors may act.

George Davey Smith, professor, clinical epidemiology.
David Gunnell, senior lecturer, epidemiology and public health.

Department of Social Medicine, University of Bristol, Bristol BS8 2PR

Jeff Holly, professor, clinical science.

Department of Surgery, University of Bristol

1. Holly JMP, Gunnell DJ, Davey Smith G. Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer? J Endocrinol 1999; 162: 321-330[Medline].

2. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998; 279: 563-566[Abstract/Full Text].

3. Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 1998; 351: 1393-1396[Medline].

4. Ma P, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 1999; 91: 620-625[Abstract/Full Text].

5. Petridou E, Dessypris N, Spanos E, Mantzoros C, Skalkidou A, Kalmanti M, et al. Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia. Int J Cancer 1999; 80: 494-496[Medline].

6. Wu X, Yu H, Amos CI, Hong WK, Spitz MR. Joint effect of insulin-like growth factors and mutagen sensitivity in lung cancer risk. J Natl Cancer Inst 2000; 92: 737-743[Abstract/Full Text].

7. Jenkins P. Cancer in acromegaly. Trends Endocrinology Metab 1998; 9: 360-366.

8. Gunnell D. Height, insulin-like growth factors and cancer risk. Growth Horm IGF Res 2000; 10(suppl A): 39-40S.

9. Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994; 78: 744-752[Medline].

10. Frankel S, Gunnell DJ, Peters TJ, Maynard M, Davey Smith G. Childhood energy intake and adult mortality from cancer: the Boyd Orr cohort study. BMJ 1998; 316: 499-504[Abstract/Full Text].

11. Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R, et al. Dietary restriction reduces insulin-like growth factor I levels, which modulated apoptosis, cell proliferation, and tumor progression in p53-defieicnt mice. Cancer Res 1997; 57: 4667-4672[Medline].

12. Sacca L, Cittadine A, Fazio S. Growth hormone and the heart. Endocr Rev 1994; 15: 555-573[Abstract].

13. Janssen JAMJL, Stolk RP, Pols HAP, Grobbe DE, Lamberts SWJ. Serum total IGF-I, free IGF-I and IGFBP-1 levels in an elderly population. Relation to cardiovascular risk factors and disease. Arterioscler Thromb Vasc Biol 1998; 18: 277-282[Abstract/Full Text].

14. Davey Smith G, Hart C, Upton M, Hole D, Gillis C, Watt G, et al. Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory and cancer mortality. J Epidemiol Commun Health 2000; 54: 97-103[Abstract/Full Text].

15. Djavan B, Bursa B, Seitz C, Soeregi G, Remzi M, Basharkhah A, et al. Insulin-like growth factor-I (IGF-I), IGF-I density and IGF/PSA ratio for prostate cancer detection. Urology 1999; 54: 603-606[Medline].

16. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of cancer -- analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000; 343: 78-85[Medline].

 

[boston789]

http://www.mindfully.org/Health/IGF-I-Cancer-Development.htm

Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression
J Natl Cancer Inst 2000; 92: 1472-1489 20sep00

2000, U.S. Department of Health and Human Services; Journal of the National Cancer Institute

Herbert Yu, Thomas Rohan

ABSTRACT: The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth. The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-I and low levels of IGFBP-3 are associated with increased risk of several common cancers, including those of the prostate, breast, colorectum, and lung. Evidence further suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth. Further investigation of the role of IGFs in linking high energy intake, increased cell proliferation, suppression of apoptosis, and increased cancer risk may provide new insights into the etiology of cancer and lead to new strategies for cancer prevention.

It has been hypothesized that cells with accelerated rates of division and proliferation are predisposed to the development of cancer [1]. Recently, a number of epidemiologic studies have shown consistently that high circulating levels of a potent mitogen, insulin-like growth factor (IGF)-I, are associated with increased risk for several common cancers, including those of the breast [2], prostate [3], lung [4], and colorectum [5]. The level of IGF-binding protein (IGFBP)-3, a major IGF-I-binding protein in serum that, in most situations, suppresses the mitogenic action of IGF-I, is inversely associated with the risk of these cancers.

Functionally, IGF-I not only stimulates cell proliferation but also inhibits apoptosis. It has now been recognized that the combination of these mitogenic and antiapoptotic effects has a profound impact on tumor growth [6]. Besides their direct effect on cancer-related cellular activities, members of the IGF family also interact with a variety of molecules that are critically involved in cancer development and progression, including the sex steroid hormones, products of tumor suppressor genes, and other growth factors. Furthermore, the expression and production of IGF-I, a key peptide hormone that is involved in regulating human growth and development, are influenced by nutrition and physical activity. These features of the IGF family underscore its potential importance in the mechanisms that underlie the roles of lifestyle and behavior in influencing cancer risk.

Several extensive reviews [719] have addressed the molecular structure and physiologic function of members of the IGF family. Here, we review briefly the molecular and biochemical aspects of each member of the IGF family and the experimental evidence for the role of IGFs in cancer, discuss the potential impact of lifestyle factors on this group of growth factors, and summarize the findings of clinical and epidemiologic studies of the IGF family in relation to cancer etiology and pathogenesis. Collectively, the evidence reviewed here provides insights into the role of mitogenic growth factors in carcinogenesis. All information used in this review was identified by searching the English-language literature in the MEDLINE(R) database.

 

[boston789]

IGFS AND CANCER: EXPERIMENTAL EVIDENCE

The possible involvement of IGFs in cancer was observed initially in cell culture experiments [128]. In vitro studies have shown consistently that members of the IGF family not only regulate the growth of various cancer cells but also interact with other cancer-related molecules. Animal experiments have suggested further that IGFs may mediate the effect of energy intake on the risk of cancer.

Direct Involvement in Cancer

IGF-I and IGF-II are strong mitogens for a wide variety of cancer cell lines, including sarcoma, leukemia, and cancers of the prostate, breast, lung, colon, stomach, esophagus, liver, pancreas, kidney, thyroid, brain, ovary, and uterus (both cervical and endometrial) [128133]. IGFs are also overexpressed in certain cancers [128]. Animal experiments [134,135] indicate that overexpression of IGF-I increases the likelihood of tumor development in certain tissues. Overexpression of IGF-II may result from loss of genomic imprinting in IGF-II, loss of function of a transcriptional repressor, or change of transcription promoter sites [130,136138]. Cancer cells with a strong tendency to metastasize have higher expression of IGF-II and IGF-IR than those with a low ability to do so [139]. The strong impact of IGF-II on cancer growth that is observed consistently in laboratory studies and the paucity of clinical and epidemiologic studies that have found an association between circulating IGF-II and cancer risk suggest that IGF-II may exert its action via paracrine rather than endocrine regulation.

The effects of IGFs on cancer cells are mediated through IGF-IR, Eliminating IGF-IR from the cell membrane, blocking the interaction of IGFs with IGF-IR, or interrupting the signal transduction pathway of IGF-IR can abolish the mitogenic action of IGFs on cancer cells [130,140142]. IGF-IR also plays a critical role in cell transformation that is induced by tumor-virus proteins and oncogene products. IGF-IR is involved not only in the induction of cell transformation but also in the maintenance of the transformed phenotype [130]. IGF-IR is overexpressed in certain cancers, and its overexpression is associated with aggressive tumors [143,144]. The hybrid receptor that binds both IGF-IR and insulin may also mediate the effect of IGFs on cancer [145,146]. A recent study [147] indicates that the insulin receptor is involved in mediating the actions of IGF-II on breast cancer.

Since IGF-IIR antagonizes the effect of IGF-II, loss of IGF-IIR function is expected in cancer. One study found cancer-related missense mutations in the IGF-IIR gene with resultant disruption of the binding of IGF-IIR to its ligand. Cancer cells that lack the ability to degrade IGF-II have been shown to have a strong growth potency [148]. Suppressing the expression of IGF-IIR yields the same effect as mutation in the IGF-IIR gene [149]. Reestablishing the function of IGF-IIR in cancer cells that lack IGF-IIR reduces cancer growth and increases apoptosis [150].

In cancer, IGFBPs regulate the action of IGFs [151156]. In most situations, the binding proteins suppress the mitogenic action of IGFs and promote apoptosis [157159]. However, because of the presence of IGFBP proteases [1719,160], two in vitro studies [161,162] have found that IGFBPs are able to stimulate the growth of cancer cells. Oh et al. [107] found that IGFBP-3 inhibited breast cancer cell growth without interacting with IGFs. Other studies [163,164] reported that IGFBP-3 could induce apoptosis of breast and prostate cancer cells without the presence of IGFs or IGF-IR.

Interactions With Other Molecules

Many molecules that are known to be involved in cancer have been found to have substantial interactions with members of the IGF family. In general, IGFs interact synergistically with other mitogenic growth factors and steroids and antagonize the effects of antiproliferative molecules in cancer cells.

In breast cancer cells, estrogens enhance the mitogenic effect of IGF-I, induce expression of IGF-I, and stimulate production of IGF-IR [165168]. Estrogens also repress synthesis of some IGFBPs in breast tissue [169,170]. In breast cancer cells, estrogens decrease the expression of IGF-IIR and increase the level of IGFBP proteases [171]. The interaction between estrogens and IGF is reciprocal. IGF-I enhances expression of estrogen receptor (ER) in breast cancer cells, and ER levels in breast tissue are associated with the levels of some IGFBPs [172,173] (see "Cancer Prognosis" section below).

Antiestrogenic agents increase the expression of IGFBPs [174176]. Tamoxifen, which is antiestrogenic in breast tissue, abolishes the effects of estrogens on IGF-I, inhibits transcription of IGF-I, and attenuates the response of IGF-IR to IGFs [177,178]

The expression of IGFs in the uterus is regulated by estrogens, and IGFBPs interfere with this process [179181]. Since tamoxifen has estrogenic effects in the uterus, synergistic interplay between tamoxifen and IGFs is also observed in endometrial cells. Tamoxifen enhances the IGF-stimulated growth of endometrial cancer cells [182]. Furthermore, there is an interaction between the signal transduction pathways of the two systems. IGF-I can enhance ER-induced gene transcription in the absence of estrogen [183]. IGFBPs, in contrast, suppress the transcriptional activation that is initiated by ERs [184]. IGFs increase the activity of estrone sulfatase, which hydrolyzes estrone sulfate to estrone [185].

Synergistic interaction is also observed between IGFs and EGF, another potent mitogen. In cervical cancer cells, EGF is able to stimulate IGF-II expression and to increase IGF-IR's response to its ligand. Increases in IGF levels, in turn, enhance the mitogenic action of EGF [186,187]. In addition, EGF can suppress the expression of IGFBP-3 and increase the availability of free IGFs, further enhancing the mitogenic signal of IGFs [188]. In prostate cancer cells, interrupting the signaling pathway for EGF suppresses not only the effect of EGF but also that of IGF-I [189].

Several studies have suggested that IGFs may mediate the effects of tumor viruses. In hepatocellular carcinoma, hepatitis B virus stimulates IGF-IR expression [190] and increases transcription of the IGF-II gene from the P3 and P4 promoters [191]. Hepatitis C virus may also be responsible for increased IGF-II transcription from fetal promoters in hepatitis C virus-related liver disease, including hepatocellular carcinoma [192].

Several antiproliferative molecules exert their actions by interfering with IGF signaling. Inhibition of breast cancer cell growth by TGF-[beta] is mediated through induction of IGFBP-3, which inhibits the mitogenic action of IGFs [98,193]. Like TGF-[beta], retinoic acid inhibits the growth of breast cancer cells by increasing IGFBP-3 expression [97,101,109]. Vitamin D and its synthetic analogues can suppress the stimulatory effect of IGFs on the growth of breast and prostate cancer cells by increasing the expression of IGFBPs and reducing the expression of IGF-IR and IGF-II [94,95,194,195].

Tumor suppressor gene products have a profound impact on the IGF family. Wild-type p53 protein induces the expression of IGFBP-3 [196], represses the transcription of IGF-II from its P3 and P4 promoters [33,197], and suppresses IGF-IR expression [70,198,199]. Not only does p53 regulate the action of IGFs but also IGFs influence p53 function. When IGF-I-induced DNA synthesis takes place in breast cancer cells, p53 loses its function by undergoing phosphorylation and relocation from the nucleus to the cytoplasm [200]. Other tumor suppressor proteins that interact with IGFs include the Wilms' tumor suppressor gene product WT1 [69,201,202], the mammary-derived growth inhibitor MDGI [203], and the tumor suppressor gene PTEN [204].

 

[boston789]

It is kinda funny that no one cares about the increased risk of cancer...

Whatever, just trying to help you people out.

 

[a creed]

Omg - Thank You!!!!!!!!!!!

 

[jerichohill]

Good Post.

 

[msam76]

 

[boston789]

I know its long...I know. But you can sift through some of the other stuff and look for what you nead. It's divided by topic. I just thought it would be good to post something just incase someone wanted to try IGF but has had a form of cancer or has a family history of it.

I for one will not be using it due to my family history and my run-in with skin cancer years ago.

 

[boston789]

Omg - Thank You!!!!!!!!!!!

sarcasm?

 

[Cauliflower Ear]

thats awful....if it is abused