Protective effect of chorionic gonadotropin on DMBA-induced mammary carcinogenesis

Ih, Russo; Koszalka, Maura A; Gimotty, PA; Russo, José

doi:10.1038/bjc.1990.268

Cited by 55 publications

(35 citation statements)

References 25 publications

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“…Our studies on the pathogenesis and prevention of chemically-induced mammary carcinogenesis have allowed us to conclude that the degree of differentiation of the mammary gland is one of the most important biological characteristics in determining its overall tumourigenic response (Russo & Russo, 1987;Russo et al, 1982Russo et al, , 1990d. Maximal susceptibility to DMBA-initiated neoplastic transformation is exhibited by mammary glands of young nulliparous females, which are characterised by the presence of undifferentiated terminal ductal structures or TEBs exhibiting a high rate of cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis

Russo

Koszalka²,

Russo³

1991

Br J Cancer

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108

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Summary Since it has been shown that pregnancy protects the mammary gland from chemically induced carcinogenesis, this study was designed with the dual purpose of determining whether treatment of young virgin rats with the placental hormone chorionic gonadotropin (hCG) mimics pregnancy-induced changes in the tumourigenic response of the mammary gland and also whether the effect induced by both pregnancy and hormonal treatments was transitory, or a more permanent one, exerting the same effect when the period of time between delivery or termination of treatment and exposure to the carcinogen is lengthened. Virgin Sprague-Dawley rats were utilised in two experimental protocols. For protocol I, 50 day-old rats were either mated (Group II), or started receiving a daily intraperitoneal injection of 100 IU hCG (Group III) at age 50.Age-matched untreated virgin rats were used as controls (Group I). Twenty-one days after either delivery or termination of treatment all the animals received an intragastric dose of 8 mg DMBA/100 gbw. For the second protocol, 50 day-old virgin rats were also mated (Group V) or were treated with hCG for 21 days (Group VI); the resting period between delivery or termination of treatment was lengthened to 63 days, at which time they received a dose of DMBA. Age-matched controls (Group IV) received DMBA only. Tumourigenesis was evaluated 24 weeks post-carcinogen administration in all the groups. Pregnancy and hCG followed by the 21-day resting period significantly depressed mammary carcinogenesis to 11% and 6% respectively, compared with 63% in control animals. When the resting period was prolonged to 63 days there was also a significant depression in adenocarcinoma incidence to 9% in pregnancy (Group V) and 7% in hCG treated (Group VI) animals respectively, vs 18% in control animals (Group IV) in which it was observed that tumour incidence was also reduced as a consequence of aging at the time of exposure to the carcinogen. These results clearly indicate that hCG is as efficient as pregnancy and significantly reduces mammary carcinogenesis, and that the protective effect of both pregnancy and hCG treatment is long-lasting and both are more efficient than aging in reducing mammary carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis

Russo

Koszalka²,

Russo³

1991

Br J Cancer

Self Cite

108

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“…Our findings demonstrated the chemopreventive and tumor suppressive effects of isoflavonedeprived soy peptide in a well-established animal Upregulated genes (＞ 2-fold) Downregulated genes (＞ 2-fold) model of breast cancer. Since DMBA-induced rat mammary gland carcinomas are reported to be similar to human breast cancers in several aspects, including histopathology, the origin of the cancers from ductal epithelial cells, and the dependency on ovarian hormones for tumor development (Russo et al, 1990), it is anticipated to have comparable effects of soy peptide on the suppression of human breast cancer development. Using various molecular and cellular analysis methods, we have demonstrated that the dietary administration of isoflavone-deprived soy peptide significantly reduced the volume, number, and weight of ductal carcinomas per multiple tumor-bearing rats, and extended the latency period of tumor development compared to the control diet + DMBA group and exerted its tumor suppressive effect by inducing apoptosis in vivo.…”

Section: Discussionmentioning

confidence: 99%

Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

et al. 2009

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During carcinogenesis, NF-κB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-κB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IκB kinase (IKK) complex that plays a central role in NF-κB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[α]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P ＜ 0.05), and extended the latency period of tumor development (8.07 ± 0.92 weeks) compared to control diet animals (10.80 ± 1.30; P ＜ 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-κB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.

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“…These observations led several independent investigators (5)(6)(7)(8) to propose and then show that administering the hormones of pregnancy (E 3 , E 2 , or hCG) leads to reduced breast cancer incidence in rats exposed to carcinogens. We have confirmed this observation and show here that the hormones of pregnancy alone are sufficient to induce elevated AFP levels in nonpregnant adult rat serum and in cultures of human liver cells.…”

Section: Discussionmentioning

confidence: 99%

“…In every case, we used MNU, although in some of the previous investigations, DMBA was used (7,8,13,17,18 Controls. The no-treatment group consisted of 30 female rats exposed to MNU without subsequent treatment, and experienced the maximal number of tumors over the course of the ensuing 4 mo.…”

Section: Hormone Treatmentsmentioning

confidence: 99%

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A Proposed Unified Mechanism for the Reduction of Human Breast Cancer Risk by the Hormones of Pregnancy

Jacobson¹,

Lemanski²,

Agarwal³

et al. 2010

Cancer Prevention Research

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Parity in women is associated with reduced lifetime risk of breast cancer, and hormones of pregnancy [estrogen (E), progesterone (P), human chorionic gonadotropin (hCG)] are implicated. Parity also reduces mammary cancer risk in carcinogen-exposed rats, and administering pregnancy hormones to these animals is similarly effective. Because pregnancy hormones are also able to stimulate cancer growth, we proposed to resolve this dichotomy by determining whether administered pregnancy hormones elicit the cancer-inhibiting agent α-fetoprotein (AFP) from the liver, which would implicate AFP as a proximal effector of hormonal anticancer activity. Accordingly, we treated groups of nitrosomethylurea-exposed rats with saline, E 3 , E 2 + P, E 3 + P, hCG, or allowed them to experience pregnancy, and then monitored mammary cancer incidence and serum levels of AFP over time. Each hormone treatment reduced mammary cancer incidence and elevated serum AFP levels. To challenge human tissues, human HepG2 liver cells in culture were treated with the same hormonal agents. Each hormone regimen increased the levels of AFP in the culture medium. Medium containing AFP elicited by hCG inhibited the E 2 -stimulated proliferation of cultured human MCF7 breast cancer cells, whereas hCG alone did not inhibit their growth. Furthermore, antibodies to AFP neutralized the growth-inhibiting effect of AFP-containing HepG2 medium. We conclude that in the treatment of carcinogen-exposed rats with the hormones of pregnancy, and by inference in women who have experienced pregnancy, that AFP is a proximal agent that inhibits mammary gland cancer. Cancer Prev Res; 3(2); 212-20. ©2010 AACR.

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Protective effect of chorionic gonadotropin on DMBA-induced mammary carcinogenesis

Cited by 55 publications

References 25 publications

Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis

Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis

Isoflavone-deprived soy peptide suppresses mammary tumorigenesis by inducing apoptosis

A Proposed Unified Mechanism for the Reduction of Human Breast Cancer Risk by the Hormones of Pregnancy

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