MECHANISMS IN ENDOCRINOLOGY: Primary HT and risk for breast cancer: a systematic review and meta-analysis

Angelousi, Anna; Anagnostou, Valsamo; Georgiopoulos, Georgios; Kontzoglou, Konstantinos

doi:10.1530/eje-11-0838

Cited by 43 publications

(52 citation statements)

References 36 publications

(121 reference statements)

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“…Clinical hypothyroidism seems to be a risk factor for several neoplasias such as liver cancer, thyroid malignancies, high-grade glioblastomas and human breast cancer (Reddi et al 2007, Polyzos et al 2008, Hassan et al 2009, Angelousi et al 2012. In contrast, increased TH levels have been associated with higher risk of esophageal, thyroid, breast and ovarian cancer development (Turkyilmaz et al 2005, Rasool et al 2014, Kunjumohamed et al 2015.…”

Section: Discussionmentioning

confidence: 99%

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

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Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metast atic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF V600E ) and, at lower levels, in TPC-1 (RET/PTC1) cells (P!0.007 and PZ0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF V600E mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P!0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 mM), MEK (U0126, 10-20 mM) or p38 (SB203580, 10-20 mM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 mM) resulted in markedly decreases in DIO3 mRNA levels. Interestingly, siRNA-mediated DIO3 silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels of DIO3 expression in PTC. Importantly, DIO3 silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness.

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Section: Discussionmentioning

confidence: 99%

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

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“…On the other hand, Shering et al (18) and Ito and Maruchi (17) observed that Japanese women with Hashimoto's thyroiditis had a higher incidence of mammary cancer than women without thyroid disease. Two recent meta-analyses showed no significant association, except for autoimmune thyroiditis which increased breast cancer risk; however, the heterogeneity of the studies analyzed precludes firm conclusions (7,22).…”

Section: Discussionmentioning

confidence: 94%

“…However, there is controversy concerning the relationship between thyroid disorders and breast cancer incidence (7). Thyroid hormones (THs) could participate directly on mammary carcinogenesis, or indirectly through their action in changes in the patterns of secretion of other hormones such as E, Pg, PRL and/or GH, among others.…”

Section: Introductionmentioning

confidence: 99%

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

et al. 2013

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Abstract. Epidemiological and in vitro data have not provided conclusive evidence concerning the involvement of thyroid hormones (THs) on mammary carcinogenesis. We used an in vivo model to assess the relationship between THs, adipose tissue and breast cancer development. Female Sprague-Dawley rats were treated with a dose of 7,12-dimethylbenz(a)anthracene (15 mg/rat) at 55 days of age and were then divided into four experimental groups: hypothyroid rats (HypoT, 0.01% 6-N-propyl-2-thiouracil in drinking water), untreated control (EUT); hyperthyroid rats (HyperT, 0.25 mg/kg/day T 4 s.c.) and vehicle-treated control rats. The latency of tumor appearance and the incidence and progression of tumors were determined. At sacrifice, blood samples were collected for hormone determinations and samples of tumor and mammary glands were obtained for immunohistological studies. HypoT rats had retarded growth and an increase in mammary fat. The latency was longer (p<0.0001), the incidence rate was lower (p<0.05) and tumor growth was slower in HypoT rats compared to EUT and HyperT rats. Mitotic index and PCNA immunostaining were similar in all groups. HypoT rats showed increased apoptosis (p<0.05) as evaluated by the apoptotic index and TUNEL staining. No differences in serum prolactin and progesterone were observed. However, circulating estradiol (E 2 ) was significantly lower in HypoT and HyperT rats. Serum leptin levels were reduced in HypoT rats even though the abdominal fat mass was similar in all groups. To note, the leptin level was higher in HypoT rats that developed mammary tumors than the level in non-tumoral HypoT rats. In conclusion, hypothyroidism altered animal growth, breast morphology, body composition, leptin secretion and serum E 2 enhancing apoptosis and, consequently, retarding mammary carcinogenesis in rats.

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“…T3 can influence the mammary gland; this involves the activation of TR present in the mammary gland inducing differentiation and lobular growth in an estrogenlike manner. However, there is controversy regarding the relationship between thyroid disorders and breast cancer (BC) incidence [19] . In this chapter, the influence of T3 on BC will be reviewed.…”

Section: Introductionmentioning

confidence: 99%

“…An inhibitory effect of iodine on BC was suggested to be attributable to its antioxidant role [60][61][62] ; however, some in vitro experiments have shown a proliferative effect of triiodothyronine on BC cell lines [63,64] . A recently conducted meta-analysis found no statistically significant association between TH replacement and BC risk [19] . One of these studies demonstrated primary hyperthyroidism as a strong protective factor against BC after adjusting for clinical parameters including TH replacement therapy [47] .…”

mentioning

confidence: 97%

Triiodothyronine and breast cancer

Síbio¹,

Oliveira²,

Moretto³

et al. 2014

WJCO

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The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Thyroid hormone; Triiodothyronine; Breast cancer; Mammary gland and metabolism Core tip: Breast cancer (BC) is a malignant tumor occurring much more frequently in women than in men; worldwide, the incidence of BC has increased markedly in recent years. It is estimated that 1.7 million women will be diagnosed with BC in 2020, marking an increase of 26%, compared to the current incidence: 1.35 million new cases annually. Countless environmental risk factors, pathological conditions, and physiological agents, as well as thyroid hormones (THs), have been involved in the development of BC. Various lines of evidence suggest tumor-promoting effects of THs. The literature contains controversial reports regarding the relationship between thyroid diseases and BC; furthermore, studies reporting both an excess of and a lack of THs may affect breast development and progression to cancer. Epidemiologically, many studies suggest that hyperthyroidism is a factor in the development of BC. Furthermore, experimental studies have shown that high levels of THs reduce the interval of multiplication of BC cell lines. Therefore, the influence of THs on BC is unclear. However, the majority of BC research suggests a relationship, primarily, when the molecular aspects of these hormones are considered in the progression of this type of tumor.De Sibio MT, de Oliveira M, Moretto FCF, Olimpio RMC, Conde SJ, Luvizon AC, Nogueira CR. Triiodothyronine and breast TOPIC HIGHLIGHT Triiodothyronine and breast cancer INTRODUCTIONThyroid hormones (THs), 3,5,3′,-triiodothyronine (T3) and thyroxine (T4), play critical roles in the differentiation, growth, metabolism, and physiological function of nearly all mammalian tissues [1,2] ; in addition, they are required for amphibian metamorphosis [3] ....

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MECHANISMS IN ENDOCRINOLOGY: Primary HT and risk for breast cancer: a systematic review and meta-analysis

Cited by 43 publications

References 36 publications

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

Triiodothyronine and breast cancer

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