The Role of Oestrogen and Progesterone Receptors in Human Mammary Development and Tumorigenesis

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2002 Sep 12

PMID 12223124

Citations 99

Authors

Elizabeth Anderson

Affiliations

Soon will be listed here.

Abstract

A relatively small number of cells in the normal human mammary gland express receptors for oestrogen and progesterone (ER and PR), and there is almost complete dissociation between steroid receptor expression and proliferation. Increased expression of the ER alpha (ERalpha) and loss of the inverse relationship between receptor expression and proliferation occur at the very earliest stages of tumorigenesis, implying that dysregulation of ERalpha expression contributes to breast tumour formation. There is evidence also for alterations in the ratio between the two PR isoforms in premalignant breast lesions. Elucidation of the factors mediating the effects of oestradiol and progesterone on development of the normal breast and of the mechanisms by which expression of the ERalpha and the PR isoforms is controlled could identify new targets for breast cancer prevention and improved prediction of breast cancer risk.

Citing Articles

Identification of Novel Progesterone Receptor (PR) Inhibitors () from Metabolites of Biotransformation Fungal: A Bioinformatics Approach.

Dourado J, Lopes S, Jimenez D, Ramos R, Ferreira I Pharmaceuticals (Basel). 2025; 18(2).

PMID: 40005951 PMC: 11858247. DOI: 10.3390/ph18020136.

Progesterone receptor is constitutively expressed in induced Pluripotent Stem Cells (iPSCs).

Manganelli M, Mazzoldi E, Ferraro R, Pinelli M, Parigi M, Aghel S Stem Cell Rev Rep. 2024; 20(8):2303-2317.

PMID: 39168923 PMC: 11554879. DOI: 10.1007/s12015-024-10776-6.

Canine Mammary Tumors as a Potential Model for Human Breast Cancer in Comparative Oncology.

Razavirad A, Rismanchi S, Mortazavi P, Muhammadnejad A Vet Med Int. 2024; 2024:9319651.

PMID: 38766503 PMC: 11101259. DOI: 10.1155/2024/9319651.

Impact of web application support versus standard management on adherence with adjuvant hormone therapy in patients treated for breast cancer: the WEBAPPAC study.

Gernier F, Grellard J, Dupont C, Castel H, Fernette M, Lahaye F BMC Cancer. 2023; 23(1):736.

PMID: 37559004 PMC: 10413707. DOI: 10.1186/s12885-023-11242-1.

Association of mutation and expression of the brother of the regulator of imprinted sites (BORIS) gene with breast cancer progression.

Akhtar M, Akhter N, Talat A, Alharbi R, Sindi A, Klufah F Oncotarget. 2023; 14:528-541.

PMID: 37235839 PMC: 10219660. DOI: 10.18632/oncotarget.28442.

References

Lawson J, Field A, Champion S, Tran D, Ishikura H, Trichopoulos D . Low oestrogen receptor alpha expression in normal breast tissue underlies low breast cancer incidence in Japan. Lancet. 1999; 354(9192):1787-8. DOI: 10.1016/s0140-6736(99)04936-3. View

Shoker B, Jarvis C, Sibson D, Walker C, Sloane J . Oestrogen receptor expression in the normal and pre-cancerous breast. J Pathol. 1999; 188(3):237-44. DOI: 10.1002/(SICI)1096-9896(199907)188:3<237::AID-PATH343>3.0.CO;2-8. View

Shoker B, Jarvis C, Clarke R, Anderson E, Hewlett J, Davies M . Estrogen receptor-positive proliferating cells in the normal and precancerous breast. Am J Pathol. 1999; 155(6):1811-5. PMC: 1866935. DOI: 10.1016/S0002-9440(10)65498-3. View

Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R . Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA. 2000; 283(4):485-91. DOI: 10.1001/jama.283.4.485. View

Ross R, Paganini-Hill A, Wan P, Pike M . Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst. 2000; 92(4):328-32. DOI: 10.1093/jnci/92.4.328. View

Anderson E, Clarke R, Howell A . Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia. 2000; 3(1):23-35. DOI: 10.1023/a:1018718117113. View

Bocchinfuso W, Korach K . Mammary gland development and tumorigenesis in estrogen receptor knockout mice. J Mammary Gland Biol Neoplasia. 2000; 2(4):323-34. DOI: 10.1023/a:1026339111278. View

Humphreys R, Lydon J, OMalley B, Rosen J . Use of PRKO mice to study the role of progesterone in mammary gland development. J Mammary Gland Biol Neoplasia. 2000; 2(4):343-54. DOI: 10.1023/a:1026343212187. View

Roger P, Sahla M, Makela S, Gustafsson J, Baldet P, ROCHEFORT H . Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors. Cancer Res. 2001; 61(6):2537-41. View

10.

Allred D, Mohsin S, Fuqua S . Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer. 2001; 8(1):47-61. DOI: 10.1677/erc.0.0080047. View

11.

Richer J, Jacobsen B, Manning N, Abel M, Wolf D, Horwitz K . Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. J Biol Chem. 2001; 277(7):5209-18. DOI: 10.1074/jbc.M110090200. View

12.

Speirs V, Skliris G, Burdall S, Carder P . Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol. 2002; 55(5):371-4. PMC: 1769648. DOI: 10.1136/jcp.55.5.371. View

13.

Conneely O, Mulac-Jericevic B, DeMayo F, Lydon J, OMalley B . Reproductive functions of progesterone receptors. Recent Prog Horm Res. 2002; 57:339-55. DOI: 10.1210/rp.57.1.339. View

14.

Speirs V . Oestrogen receptor beta in breast cancer: good, bad or still too early to tell?. J Pathol. 2002; 197(2):143-7. DOI: 10.1002/path.1072. View

15.

Skliris G, Parkes A, Limer J, Burdall S, Carder P, Speirs V . Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue. J Pathol. 2002; 197(2):155-62. DOI: 10.1002/path.1077. View

16.

Mote P, Bartow S, Tran N, Clarke C . Loss of co-ordinate expression of progesterone receptors A and B is an early event in breast carcinogenesis. Breast Cancer Res Treat. 2002; 72(2):163-72. DOI: 10.1023/a:1014820500738. View

17.

Kumar V, Green S, Stack G, Berry M, Jin J, Chambon P . Functional domains of the human estrogen receptor. Cell. 1987; 51(6):941-51. DOI: 10.1016/0092-8674(87)90581-2. View

18.

Key T, Pike M . The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol. 1988; 24(1):29-43. DOI: 10.1016/0277-5379(88)90173-3. View

19.

Clarke C, Sutherland R . Progestin regulation of cellular proliferation. Endocr Rev. 1990; 11(2):266-301. DOI: 10.1210/edrv-11-2-266. View

20.

Vegeto E, Shahbaz M, Wen D, Goldman M, OMalley B, McDonnell D . Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol. 1993; 7(10):1244-55. DOI: 10.1210/mend.7.10.8264658. View