Androgen regulation of prolactin‐receptor gene expression in MCF‐7 and MDA‐MB‐453 human breast cancer cells

Ormandy, Christopher J.; Kelly, Paul A.; Sutherland, Robert L.

doi:10.1002/ijc.2910500519

Cited by 28 publications

(17 citation statements)

References 33 publications

(30 reference statements)

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“…Progesterone inhibits PRL-mediated expression of milk protein in mammary epithelial cells by an interaction of progesterone receptor with the signal transducer and transcription activator STAT5 (Gass et al 1998). 17 -Estradiol has been reported to increase milk protein expression by increasing PRL receptors (Mizoguchi et al 1997, Ormandy et al 1992a.…”

Section: Discussionmentioning

confidence: 99%

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

Baratta

Grolli²,

Poletti

et al. 2000

Journal of Endocrinology

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Androgens have been found in mammary epithelium and in milk throughout the cycle of the mammary gland in vivo. The aim of this study was to investigate the possible role of these substances in mammary epithelial growth and differentiation in the mouse HC11 cell line. Cells were stimulated with testosterone, dihydrotestosterone, androstenedione and 5 -androstane-3 ,17 -diol at concentrations ranging between 0·3 nM and 30 nM. Cyproterone acetate or flutamide, androgen receptor antagonists, (3 µM) were used to block specific androgen effects. Proliferative effects were measured by an MTT (tetrazolium blue) conversion test and [ 3 H]thymidine uptake. HC11 cells were transfected with p cCAT, a chimeric rat -casein gene promoter-chloramphenicol acetyl transferase (CAT) gene construct and CAT ELISA was used to determine gene expression. RT-PCR was performed to detect androgen receptor expression. After 24, 48 and 72 h androgens significantly (P<0·05) increased proliferation. Androgen antagonists significantly (P<0·05) reduced the proliferative effects. Furthermore androgens potentiated the lactogenic effect of prolactin, insulin and dexamethasone (P<0·05). Finally, the androgen receptor gene was expressed in both proliferating and differentiated HC11 cells. These observations lead us to hypothesize an activity of this class of steroids in mammary physiology. In particular, androgens stimulate cell proliferation and -casein gene expression; this influence appears to be mediated by androgen receptors.

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Section: Discussionmentioning

confidence: 99%

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

Baratta

Grolli²,

Poletti

et al. 2000

Journal of Endocrinology

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“…We have previously reported that progestin treatment of T-47D and MCF-7 cells increased the level of PRLR binding activity (Murphy et al, 1986) and that this effect was progesterone receptor mediated (Ormandy et al, 1992). In the current work, the molecular basis for these observations was investigated.…”

Section: Discussionmentioning

confidence: 93%

The Effect of Progestins on Prolactin Receptor Gene Transcription in Human Breast Cancer Cells

Ormandy¹,

Graham²,

Kelly³

et al. 1992

DNA and Cell Biology

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The sex steroid hormone progesterone modulates the developmental and lactogenic activity of prolactin in the mammary gland. Regulation of the level of prolactin receptor (PRLR) provides one possible mechanism by which this may occur, prompting this investigation of the molecular mechanisms involved in progestin regulation of prolactin receptor levels. Treatment of T-47D and MCF-7 human breast cancer cells with 10 nM of the synthetic progestin ORG 2058 for 24 hr resulted in an increase in all four PRLR mRNA transcripts detected. The effect of ORG 2058 was shown in T-47D cells to be time- and concentration-dependent and resulted in an approximate two-fold increase in PRLR mRNA after 24 hr of treatment with 10 nM or 100 nM ORG 2058. Nuclear run-on assays indicated that ORG 2058 increased the rate of T-47D PRLR gene transcription at all times between 1 hr and 28 hr of treatment. The protein synthesis inhibitors cycloheximide and puromycin abrogated the induction of PRLR gene transcription at 1 hr and 2 hr, which demonstrated that on-going protein synthesis was required for the ORG 2058 effect and suggested that progestins may exert some transcriptional effects via the induction of an intermediary protein. These experiments demonstrated that progestin induced a transcriptionally based increase in PRLR gene expression and provided a mechanism by which progesterone may modulate the mitogenic activity of prolactin during mammary gland development.

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“…This consideration gains support from the fact that prolactin exerts a considerable influence on chemically induced mammary carcinogenesis [107][108][109]. Moreover, several in vitro studies also show that androgens induce expression of the prolactin receptor [110] as well as stimulate expression and secretion of prolactin in uterine stromal cells [111]. Thus, the lactational alterations in neonatally androgenized female rats may be due to increased function of prolactin-prolactin receptor signaling.…”

Section: Uses Of Androgens In Womenmentioning

confidence: 99%

“…Since progesterone has a complicated influence on the mammary epithelia, including both growth stimulation and inhibition [287], it remains possible that the reported dual functions of androgens may actually be a reflection of their progestational effects. In addition, androgens have been shown to stimulate expression and secretion of prolactin from uterine stromal cells [111] and to induce expression of the prolactin receptor in human breast cancer cells [110]. Neonatal androgenization also increases the secretion of prolactin from pituitary during adulthood [94;106].…”

Section: Uses Of Androgens In Womenmentioning

confidence: 99%

Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process

Liao¹

2001

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructior's, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and ABSTRACT (Maximum 200 Words)This project aims to elucidate the cell cycle basis on which c-myc oncogene induces mammary carcinogenesis and transforming growth factor o (tgfcx) promotes the process. Conduction of this training project will help the P.1. to develop his career in breast cancer research. Data obtained so far have shown that c-myc transgenic mammary tumors may develop specific foci that are more aggressive than their adjacent tumor areas and thus represent a second stage of tumor progression. c-Myc may induce E2F1 and cyclin A2 to initiate the tumor development, whereas overexpression of cyclins DI and E may occur as later events to promote tumor progression to a more aggressive phenotype. TGFcc may enhance c-Myc-induced mammary carcinogenesis by inducing cyclin DI and facilitating the loss of pRB expression, resulting in an earlier development of more aggressive tumors in tgfa/c-myc double transgeneic mice, compared to the c-myc tumors. These findings in the transgenic animals may have relevance to human breast cancer. INTRODUCTION:This subject of study aims to elucidate the cell cycle basis on which c-myc oncogene initiates mammary carcinogenesis and transforming growth factor (X (tgfa) promotes the process. Conduction of this training project will help the P.I., Dr. Dezhong Liao, to develop his career in breast cancer research. This research project has four tasks, each of which is consisted of two parts, i.e. in vivo studies with transgenic mice and in vitro studies with cultured cells. The four tasks are: "* Task 1. Study whether expression of E2F1 and cyclin A2 is induced to mediate mammary cancer formation in c-myc mice. (Months 1-15). "* Task 2. Investigate whether c-myc initially suppresses cyclin DI expression, but overexpression of cyclins DI and E occurs as later events to facilitate progression of tumors to faster growing phenotypes. (Months 1-15) "* Task 3. Study the mechanisms and the roles of overexpression of cyclins DI and E in mammary carcinogenesis in TGFc/c-myc mice. . "* Task 4. Investigate the mechanisms for the loss of pRB during mammary carcinogenesis in myc and TGFcu/c-myc mice. BODY:1. In vivo animal experiments on the cell cycle basis of c-myc-induced, tgfu.-enhanced mouse mammary carcinogenesis: We have actually started the project since this proposal was submitted to DOD in June of 1999, about one year earlier than the time when the award was started. During the past two years, ...

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Androgen regulation of prolactin‐receptor gene expression in MCF‐7 and MDA‐MB‐453 human breast cancer cells

Cited by 28 publications

References 33 publications

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

Role of androgens in proliferation and differentiation of mouse mammary epithelial cell line HC11

The Effect of Progestins on Prolactin Receptor Gene Transcription in Human Breast Cancer Cells

Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process

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