<i>In vitro</i> effects of growth hormone (GH) and insulin‐like growth factor I and II (IGF‐I and ‐II) on chromosome fragility and p53 protein expression in human lymphocytes

Cianfarani, Stefano; Tedeschi, Bruna; Germani, Daniela; Prete, Salvatore Pasquale; Rossi, Paolo; Vernole, Patrizia; Caporossi, Daniela; Boscherini, B

doi:10.1046/j.1365-2362.1998.00247.x

Cited by 34 publications

(20 citation statements)

References 37 publications

(47 reference statements)

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“…Although there is some in vitro experimental evidence of a possible association between GH1 and breast carcinoma, [7][8][9][10] no positive epidemiologic findings have been reported since 1985, when a small casecontrol study reported an elevated concentration of GH1 in sera obtained from patients with breast carcinoma. 11 Although two recent prospective epidemiologic studies demonstrated that high circulating GH1 concentrations and GH1 treatment are significantly associated with an increased risk of malignancy, 21,22 no association with breast carcinoma risk was found.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that GH1 increases expression of insulinlike growth factor I (IGF-I) and IGF-I binding protein 3 (IGFBP-3), 2,4 both of which may be related to breast carcinoma risk. 2 It also has been reported that GH1 may increase chromosome fragility both in vitro and in vivo 7 and may increase the expression and transcriptional activity of the oncogene HOXA1. 8 It was found that GH1 gene expression and GH1 protein concentrations were much higher in progressive proliferative disorder tissue samples compared with normal mammary gland tissue samples.…”

mentioning

confidence: 98%

“…8 It was found that GH1 gene expression and GH1 protein concentrations were much higher in progressive proliferative disorder tissue samples compared with normal mammary gland tissue samples. 9 Transgenic mice that overexpressed the GH1 gene were susceptible to developing mammary tumors, 7 and breast tumor growth in GH1 knockout mice was reduced dramatically. 10 Increased serum levels of GH1 in patients with breast carcinoma also have been reported.…”

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confidence: 99%

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Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma

Ren

Cai

Shu

et al. 2004

Cancer

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BACKGROUNDIn addition to possessing many physiologic functions, human growth hormone‐1 (GH1) has been shown in recent in vitro and in vivo experiments to induce malignant disease, including breast carcinoma. The authors investigated the association of breast carcinoma with genetic polymorphisms in the GH1 gene in the Shanghai Breast Cancer Study.METHODSIncluded in the current investigation were 1193 women with breast carcinoma (case patients) and 1310 healthy women from the same community (control patients) who completed in‐person interviews and provided blood samples. Genetic polymorphisms in the proximal promoter region (nucleotide [nt] −162 to nt +148 relative to the transcription start site of the GH1 gene) were searched and confirmed by resequencing DNA samples from 43 study participants. A novel polymorphism, a transition from adenine to guanine at nt 69 (A69G), was identified. Samples from all participants were genotyped with TaqMan 5′ nuclease assays for five common single‐nucleotide polymorphisms (SNPs)—four in the proximal region (A‐75G, G‐57T, A‐6G, and A69G) and one in intron 4 (T1169A).RESULTSThe frequencies of occurrence for the minor alleles in these polymorphic sites were 0.04, 0.60, 0.24, 0.03, and 0.34, respectively, in the control group; these frequencies were comparable to those observed in the case group. After adjusting for potential confounding factors, none of the SNPs investigated in this study showed a statistically significant association with breast carcinoma risk. This null association was found for both younger women (age < 45 years) and older women (age ≥ 45 years). GH1 gene haplotypes were assessed using SNP data and were analyzed in relation to breast carcinoma risk. Again, none of the haplotypes were associated with breast carcinoma risk.CONCLUSIONSThe results of the current study suggest that genetic polymorphisms in the proximal promoter region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma risk in Chinese women. Cancer 2004. © 2004 American Cancer Society.

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Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma

Ren

Cai

Shu

et al. 2004

Cancer

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“…Suggested hypotheses include genetic factors, energy intake in early life, and exposure to sex and growth hormones. For instance, insulin-like growth factor-I is associated with height and also inhibits apoptosis of damaged cells and stimulates cell turnover and cell proliferation (8,72,73). Insulin-like growth factor-I was associated with an increased risk of ovarian cancer before age 55 in one study (74).…”

Section: Anthropometry and Ovarian Cancer Cancer Epidemiol Biomarkersmentioning

confidence: 97%

Height, Body Mass Index, and Ovarian Cancer: A Pooled Analysis of 12 Cohort Studies

Schouten

Rivera

Hunter

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

135

105

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Background: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent. Methods: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified. To summarize associations, study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Results: Women with height z1.70 m had a pooled multivariate RR of 1.38 [95% confidence interval (95% CI), 1.16-1.65] compared with those with height <1.60 m. For the same comparison, multivariate RRs were 1.79 (95% CI, 1.07-3.00) for premenopausal and

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“…However, it is plausible that mammotrophic factors such as hGH in executing their physiological roles may simply utilize CHOP to mediate cell survival and that the subsequent failure to undergo programmed cell death, in situations of cellular injury associated with DNA damage, would result in carcinoma (72). It is therefore interesting that the DNA-damaging effect of bleomycin in human lymphocytes is enhanced by hGH (73); and hGH and the related hormone prolactin have both been implicated in the development of mammary carcinoma (74). It is also interesting that GH itself has also been reported to be both mitogenic and growth inhibitory depending on the cellular context (75).…”

Section: Effect Of Chop Overexpression In Mammary Carcinoma Cells On mentioning

confidence: 99%

Autocrine Human Growth Hormone (hGH) Regulation of Human Mammary Carcinoma Cell Gene Expression

Mertani

Zhu

Goh

et al. 2001

Journal of Biological Chemistry

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By use of cDNA array technology we have screened 588 genes to determine the effect of autocrine production of human growth hormone (hGH) on gene expression in human mammary carcinoma cells. We have used a previously described cellular model to study autocrine hGH function in which the hGH gene or a translationdeficient hGH gene was stably transfected into MCF-7 cells. Fifty two of the screened genes were regulated, either positively (24) or negatively (28), by autocrine production of hGH. We have now characterized the role of one of the up-regulated genes, chop (gadd153), in the effect of autocrine production of hGH on mammary carcinoma cell number. The effect of autocrine production of hGH on the level of CHOP mRNA was exerted at the transcriptional level as autocrine hGH increased chloramphenicol acetyltransferase production from a reporter plasmid containing a 1-kilobase pair fragment of the chop promoter. The autocrine hGH-stimulated increase in CHOP mRNA also resulted in an increase in CHOP protein. As a consequence, autocrine hGH stimulation of CHOP-mediated transcriptional activation was increased. Stable transfection of human CHOP cDNA into mammary carcinoma cells demonstrated that CHOP functioned not as a mediator of hGH-stimulated mitogenesis but rather enhanced the protection from apoptosis afforded by hGH in a p38 MAPK-dependent manner. Thus transcriptional up-regulation of chop is one mechanism by which hGH regulates mammary carcinoma cell number.

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In vitro effects of growth hormone (GH) and insulin‐like growth factor I and II (IGF‐I and ‐II) on chromosome fragility and p53 protein expression in human lymphocytes

Abstract: These results indicate that the DNA-damaging effect of BLM is amplified by GH and, more markedly, IGF-I and -II. IGF-I and -II also stimulate p53 protein expression that, taking part in DNA repair, may counteract the IGF action on genome stability.

Cited by 34 publications

References 37 publications

Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma

Genetic polymorphisms in the human growth hormone‐1 gene (GH1) and the risk of breast carcinoma

Height, Body Mass Index, and Ovarian Cancer: A Pooled Analysis of 12 Cohort Studies

Autocrine Human Growth Hormone (hGH) Regulation of Human Mammary Carcinoma Cell Gene Expression

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