Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas

Waliszewski, Przemysław; Blaszczyk, Miroslawa; Woliñska-Witort, Ewa; Drews, M; Snochowski, Marek; Hurst, Robert E.

doi:10.1002/(sici)1096-9098(199701)64:1<3::aid-jso2>3.0.co;2-g

Cited by 49 publications

(32 citation statements)

References 36 publications

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“…41 This has been claimed to be due to ERb promoter methylation occurring during the malignant transformation. [42][43][44] In the case of breast, colon and prostate cancer, as well as brain astrocytic tumors, ERb expression has been correlated to a higher tumor differentiation grade, in line with its antiproliferative and differentiating effects. [45][46][47][48] It is of interest that malignant lymphoid cells, as described for the cell lines used in this report, retain ERb expression.…”

Section: Discussionmentioning

confidence: 96%

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

et al. 2011

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Estrogen receptor b (ERb) is expressed in immune cells and studies have suggested an antiproliferative function of ERb. We detected ERb expression in murine T-and human B-cell lymphoma cell lines and analyzed the effects of estradiol and selective ERb agonists on lymphoma growth in culture and in vivo. Treating the cells with estradiol had minor effects on cell growth, whereas the selective ERb agonists diarylpropionitrile (DPN) and KB9520 showed a strong antiproliferative effect. When grafting mice with murine T-cell lymphoma cells, male mice developed larger tumors compared with female mice, a difference that was abolished following ovariectomy, showing estrogen-dependent growth in vivo. To investigate whether lymphoma growth may be inhibited in vivo by ERb agonist treatment, mice grafted with murine lymphoma cells were treated with DPN or KB9520. Both ERb-selective agonists strongly inhibited lymphoma growth. The reduced tumor size seen following either DPN or KB9520 treatment was due to reduced proliferation and increased apoptosis. Our results show an ERb ligand-dependent antiproliferative effect of lymphoma cells expressing endogenous ERb and that lymphoma cell growth in vivo can efficiently be inhibited by ERb agonists. This suggests that ERb agonists may be useful in the treatment of lymphomas.

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Section: Discussionmentioning

confidence: 96%

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

et al. 2011

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“…Recent studies suggested a protective function of androgens in the colon (23,24). AR expressions have been detected in the colorectal mucosa of experimental animals and humans (25,26). Positive AR expressions were observed in 42.7% of colorectal cancer foci and 81.3% of normal mucosa in our study; but this percent was different from that of two studies, which reported lower AR expression in neoplastic mucosa than that in normal colonic mucosa (17,27).…”

Section: Discussionmentioning

confidence: 99%

Polymorphic CAG Repeat and Protein Expression of Androgen Receptor Gene in Colorectal Cancer

Huang

Wang

Song

et al. 2015

Molecular Cancer Therapeutics

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Although somatic alterations in CAG repeats in the androgen receptor (AR) gene have been suggested to predispose to colorectal cancer, less is known about AR in colorectal cancer carcinogenesis. Because of lack of relevant analysis on CAG repeat length and AR expression in colorectal cancer, we aimed to investigate the prognostic value of polymorphic CAG and protein expression of the AR gene in patients with colorectal cancer. A case-control study was carried out on 550 patients with colorectal cancer and 540 healthy controls to investigate whether polymorphic CAG within the AR gene is linked to increased risk for colorectal cancer. Polymorphic CAG and AR expression were analyzed to clarify their relationship with clinicopathologic and prognostic factors in patients with colorectal cancer. The study showed that the AR gene in patients with colorectal cancer had a longer CAG repeat sequence than those in the control group, as well as increased risk for colorectal cancer among females (P ¼ 0.013), males (P ¼ 0.002), and total colorectal cancer population (P < 0.001), respectively. AR expression exhibited a significant difference in long CAG repeat sequence among males (P < 0.001), females (P < 0.001), and total colorectal cancer study population (P < 0.001). Both long CAG repeat sequence and negative AR expression were associated with a short 5-year overall survival (OS) rate in colorectal cancer. Long CAG repeat sequences and the absence of AR expression were closely related to the development of colorectal cancer. Both long CAG and decreased AR expression were correlated with the poor 5-year OS in patients with colorectal cancer.

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“…Since ERa is reported to be minimally expressed in normal colon mucosa and colon cancer cells (Waliszewski et al 1997, Campbell-Thompson et al 2001, the effects of estrogen on colon cancer susceptibility may be mediated by ERb. Using semiquantitative RT-PCR, Campbell-Thompson et al (2001) showed that ERb is the predominant ER subtype in the human colon, and that decreased ERb1 (ERbwt) and ERb2 (ERbcx) mRNA levels are associated with colonic tumorigenesis in women.…”

Section: Endocrine-related Cancer (2004) 11 537-551mentioning

confidence: 99%

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

Bardin¹,

Boulle²,

Lazennec³

et al. 2004

Endocr Relat Cancer

386

308

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The characterization of estrogen receptor beta (ERb) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and the mitogenic effects of estrogen in these tissues (such as breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERb expression in cancer as compared with benign tumors or normal tissues, whereas ERa expression persists. The loss of ERb expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERa target genes by ERb or ERb-specific gene induction could explain that ERb has a differential effect on proliferation as compared with ERa. ERb may exert a protective effect and thus constitute a new target for hormone therapy, such as ligand specific activation. The potential distinct roles of ERa and ERb expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review.

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Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas

Cited by 49 publications

References 36 publications

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

Polymorphic CAG Repeat and Protein Expression of Androgen Receptor Gene in Colorectal Cancer

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

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