The mammary gland is the functional structure of the female breast and develops initially as a skin specialization. Breast growth and appearance in male and female children are virtually identical prior to puberty. At puberty females, under the influence of mainly sex hormone signaling, undergo a series of growth changes. Breast growth after puberty is defined by the "Tanner Stages". (More? Tanner Stages)
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Model of Mammary Development |
Tanner Stages |
In pregnancy, an additional series of signals leads to further changes in breast structure. Finally at menopause, changes in sex hormone secretion can once again alter breast structure.
The breast also associated with oncogenesis (breast cancer). Research in this area has been aided by the discovery in 1994 of the two breast cancer susceptibility genes (BRCA1, BRCA2). (More? Breast Cancer) There is some developing evidence that modification of stem cells (progenitor cells) that exist in the mammary gland may also contribute to neoplasms (cancer).
See also postnatal development notes Normal Development - Milk.
Page Links: Introduction | Some Recent Findings | Development Overview | Embryonic Stages | Mammary Model | Tanner Stages | Mammary Glands Pregnancy | Abnormalities | Breast Cancer | References | Glossary
Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A. 2008 Jan 29;
"Although it is well established that women with germ-line mutations in the BRCA1 gene have a greatly increased lifetime incidence of breast and ovarian cancer, the molecular mechanisms responsible for this tissue-specific carcinogenesis remain undefined. ...Because BRCA1 also plays a role in DNA repair, our work suggests that loss of BRCA1 may result in the accumulation of genetically unstable breast stem cells, providing prime targets for further carcinogenic events. "
Robinson GW. Cooperation of signalling pathways in embryonic mammary gland development. Nat Rev Genet. 2007 Dec;8(12):963-72. Review.
Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell. 2006 Dec 1;127(5):1041-55. (More? OMIM - GATA3)
"The GATA family of transcription factors plays fundamental roles in cell-fate specification. ...We identified GATA-3 as the most highly enriched transcription factor in the mammary epithelium of pubertal mice. ...suggests that GATA-3 actively maintains luminal epithelial differentiation in the adult mammary gland"
Cho KW, Kim JY, Song SJ, Farrell E, Eblaghie MC, Kim HJ, Tickle C, Jung HS. Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci U S A. 2006 Oct 27
"...the same DV boundary may not only position limbs and determine coat color but also position mammary glands. Furthermore, Bmp signaling appears to be a fundamental feature of DV patterning."
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Mouse Mammary Development (A) Late E10/E11 as cells initially aggregate into elliptical shape. (B) E11.5 epidermal thickening. (C) E12.0 at hillock stage. (D) E13.0 at spherical bud stage. (E) E14.5 at light bulb stage. (Image: Signalling Pathways Implicated in Early Mammary Gland Morphogenesis and Breast Cancer Howard B, Ashworth A PLoS Genetics Vol. 2, No. 8, e112 doi:10.1371/journal.pgen.0020112) |
(Image: Signalling Pathways Implicated in Early Mammary Gland Morphogenesis and Breast Cancer Howard B, Ashworth A PLoS Genetics Vol. 2, No. 8, e112 doi:10.1371/journal.pgen.0020112)
In 1976 Tanner and Whitehouse established a series of descriptive stages for primary and secondary sexual characteristic development at puberty. The female secondary sex characteristics of breast development were divided into five numbered (1 - 5) "Tanner Stages".
Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976 Mar;51(3):170-9.
During pregnancy raised estrogens and progesterone stimulate gland development and hemispherical shape occurs due to fat deposition. After birth, neonatal lactation supports further growth/development.
Abnormalities occur in approximately 1% of female population and include in both sexes:
Gynecomastia ((Greek, gyne = woman, mastos = breast) is the excessive development of the male breast, which can occur transiently in puberty or due to other (hormonal) abnormalities.
In 1994, two breast cancer susceptibility genes were identified BRCA1 on chromosome 17 and BRCA2 on chromosome 13
When an individual carries a mutation in either BRCA1 or BRCA2, they are at an increased risk of being diagnosed with breast or ovarian cancer at some point in their lives. Normal function of these genes was to participate in repairing radiation-induced breaks in double-stranded DNA. It is though that mutations in BRCA1 or BRCA2 might disable this mechanism, leading to more errors in DNA replication and ultimately to cancerous growth. (text modified from: NCBI genes and disease)
Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS. BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci U S A. 2008 Jan 29;
"Although it is well established that women with germ-line mutations in the BRCA1 gene have a greatly increased lifetime incidence of breast and ovarian cancer, the molecular mechanisms responsible for this tissue-specific carcinogenesis remain undefined. ...Because BRCA1 also plays a role in DNA repair, our work suggests that loss of BRCA1 may result in the accumulation of genetically unstable breast stem cells, providing prime targets for further carcinogenic events. "
Breast Cancer Detection - reduce mortality is through early detection (general screening of the population for BRCA1 and BRCA2 is not yet recommended). New strategies to find anti-cancer drugs are constantly being developed. The latest, called 'synthetic lethal screening' looks for new drug targets in organisms such as yeast and fruit flies. In the same way that studies in yeast recently helped to identify the functions of BRCA1 and BRCA2, it is thought that drugs that work in more primative organisms will also be applicable to humans. (text modified from: NCBI genes and disease)
Links: OMIM - BRCA1 | OMIM - BRCA2
Reviews
Robinson GW. Cooperation of signalling pathways in embryonic mammary gland development. Nat Rev Genet. 2007 Dec;8(12):963-72. Review.
De Silva NK, Brandt ML. Disorders of the breast in children and adolescents, Part 1: Disorders of growth and infections of the breast. J Pediatr Adolesc Gynecol. 2006 Oct;19(5):345-9.
Domchek SM, Weber BL. Clinical management of BRCA1 and BRCA2 mutation carriers. Oncogene. 2006 Sep 25;25(43):5825-31.
Tanner JM. Normal growth and techniques of growth assessment. Clin Endocrinol Metab. 1986 Aug;15(3):411-51.
Articles
Kouros-Mehr H, Slorach EM, Sternlicht MD, Werb Z. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell. 2006 Dec 1;127(5):1041-55.
Cho KW, Kim JY, Song SJ, Farrell E, Eblaghie MC, Kim HJ, Tickle C, Jung HS. Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci U S A. 2006 Oct 27
Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976 Mar;51(3):170-9.
Search PubMed: Feb 2007 "breast development" 18,066 reference articles of which 4,449 were reviews.
Search PubMed Now: breast development | female puberty
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This page introduces the specialized skin structures we know as breasts. These features define us and other animals as "mammals" as we depend on lactation of mild formed by mammary glands for early growth and nutrition.
There is also much research in this area as breasts are also the site of one of the major forms of female oncogenesis, breast cancer. Note though, that breast cancer can also occur in males.
Please email Dr Mark Hill if you wish to make a comment about this current project.