Endocrine Regulation of HOX Genes

Daftary, Gaurang S.; Taylor, Hugh S.

doi:10.1210/er.2005-0018

Cited by 279 publications

(234 citation statements)

References 246 publications

(153 reference statements)

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“…Studies on xenoestrogens, such as methoxychlor (MXC) and bisphenoyl A (BPA), have shown that exposure to these chemicals also alters the Hoxa10 expression in female reproductive tract (Block et al 2000;Suzuki et al 2004;Fei et al 2005;Markey et al 2005;Sugiura-Ogasawara et al 2005;Daftary and Taylor 2006;Smith and Taylor 2007). MXC is a pesticide and this chemical is associated with female reproductive defects after either prenatal or postnatal exposure.…”

Section: Estrogens and Progesterone Regulate Hox Gene Expression In Tmentioning

confidence: 99%

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

Taylor

2015

Cold Spring Harb Perspect Med

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186

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HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Mü llerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility.

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Section: Estrogens and Progesterone Regulate Hox Gene Expression In Tmentioning

confidence: 99%

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

Taylor

2015

Cold Spring Harb Perspect Med

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186

158

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“…23). Interest in the functional role of HOXB13 in tumorigenesis originated from our previous observation that HOXB13 is overexpressed in tamoxifen-resistant human breast cancers.…”

Section: Hoxb13 Abrogates the Antagonistic Effect Of Tamoxifenmentioning

confidence: 99%

HOXB13 promotes ovarian cancer progression

Miao

Wang

Provencher

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

102

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Deregulated expression of HOXB13 in a subset of estrogen receptor-positive breast cancer patients treated with tamoxifen monotherapy is associated with an aggressive clinical course and poor outcome. Because the ovary is another hormone-responsive organ, we investigated whether HOXB13 plays a role in ovarian cancer progression. We show that HOXB13 is expressed in multiple human ovarian cancer cell lines and tumors and that knockdown of endogenous HOXB13 by RNA interference in human ovarian cancer cell lines is associated with reduced cell proliferation. Ectopic expression of HOXB13 is capable of transforming p53 ؊/؊ mouse embryonic fibroblasts and promotes cell proliferation and anchorage-independent growth in mouse ovarian cancer cell lines that contain genetic alterations in p53, myc, and ras. In this genetically defined cell line model of ovarian cancer, we demonstrate that HOXB13 collaborates with activated ras to markedly promote tumor growth in vivo and that HOXB13 confers resistance to tamoxifen-mediated apoptosis. Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer.T he HOX family of homeobox genes is an important group of developmental transcriptional regulators that are critical for various aspects of differentiation and morphogenesis (1). Similar to other genes that regulate normal growth and differentiation, HOX genes have been implicated in different aspects of the oncogenic process, because ectopic expression of HOX genes promotes cellular transformation in vitro and tumorigenesis in vivo (2). Of particular interest to human tumorigenesis is the observation that various human tumors including breast, colon, prostate, and lung carcinomas display altered HOX gene expression (3-7). Several HOX family members have been implicated in ovarian cancer differentiation (8, 9), although it is unknown whether HOX genes play a direct role in ovarian cancer progression.We recently demonstrated that dysregulated HOXB13 expression in human breast cancer is directly correlated with poor clinical outcome in estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen monotherapy (10). In preliminary functional studies, we demonstrated that ectopic expression of HOXB13 in a nontransformed human mammary epithelial cell confers increased cell migration and invasion, two characteristics associated with tumor aggressiveness (10). Consistent with a possible role in human tumorigenesis, others have recently shown that HOXB13 is overexpressed in human endometrial, ovarian, and cervical carcinomas and that overexpression of HOXB13 is associated with the invasiveness of ovarian and endometrial cancer cells (11-13). Collectively, these observations suggest that HOXB13 may play an important role in tumors arising from endocrine-responsive organs. Herein, we characterized the expression of HOXB13 in ovarian cancer cell lines and tumors. Furthermore, we investigated the potential growth modulatory role of HOXB13 in vitro and in a genetically defined mouse mod...

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“…These changes occur through the ability of sex hormones to alter the expression of genes encoding the structural information of soft tissues and bone components in terminal limb buds and other sexually selected structures during sensitive phases coinciding with hormone production (Phoenix et al, 1959;Block et al, 2000;Daftary and Taylor, 2006;Zheng and Cohn, 2011). The overarching theory is that 2D:4D acts as a "readout" of the programming effects of sex hormones on the fetal brain and body, and that this period may impact adult sex-linked traits and behaviors.…”

Section: Introductionmentioning

confidence: 99%

Females Have Larger Ratio of Second‐to‐Fourth Digits Than Males in Four Species of Salamandridae, Caudata

Kaczmarski

Kubicka

Tryjanowski

et al. 2015

The Anatomical Record

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Digit ratio (2D:4D) denotes the relative length of the second and fourth digits. It is considered to be a suitable biomarker of the in utero balance of fetal sex hormones, which affect early development of individua ls behavioral and morphological characteristics. In recent decades, digit ratio attracted a great attention in biology and psychology. However, for unmasking the biological basis of the phenomenon, extensive studies on nonhuman animals are necessary. Despite it was hypothesized that digit ratio is well conserved in all Tetrapoda, and there exist studies on mammals, birds, and reptiles, there are only two such study on anuran amphibians. Therefore, the aim of this study is to investigate the 2D:4D in the most basal salamanders, Caudata. We have studied digit ratio in four species of newts: Triturus cristatus, Mesotriton alpestris, Lissotriton montandoni, and Lissotriton vulgaris, using museum collection. We used computerized measuring of each limbs photos. We have found out that, in M. alpestris, females 2D:4D of all four limbs were significantly larger than in males. In L. montandoni and L. vulgaris, only 2D:4D of rear limbs significantly differed, in females being larger. In T. cristatus, digit ratios of males and females did not statistically differ. Thus, the results confirmed our hypothesis that at least in M. alpestris, L. montandoni, and L. vulgaris, females seem to have larger 2D:4D comparing to males, the pattern known from most mammals and opposite to birds, reptiles and anuran amphibians.

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Endocrine Regulation of HOX Genes

Cited by 279 publications

References 246 publications

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

HOXB13 promotes ovarian cancer progression

Females Have Larger Ratio of Second‐to‐Fourth Digits Than Males in Four Species of Salamandridae, Caudata

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