Genomic signature and susceptibility to breast cancer

Early parity is associated with a pronounced decrease in the risk of breast cancer, and additional live births reduce the risk even move. The protection afforded by early full-term pregnancy in women can be explained by the higher degree of differentiation of the mammary gland, which eliminates type 1 stem cells and creates a second type of stem cell (stem cell 2) that is able to metabolize carcinogens and repair DNA damage more efficiently than cells of the nulliparous breast. All though differentiation significantly reduces cell proliferation in the mammary gland, the epithelium remains capable of responding to a given stimulus, such as a new pregnancy. Under these circumstances, the cells that are stimulated to proliferate are derived from structures that have already been primed by the first cycle of differentiation. However, if the shift from stem cell 1 to stem cell 2 has not been completed, a sufficiently powerful carcinogenic stimulus may overburden the system, and successfully initiate a neoplastic process. Incomplete differentiation of this type may explain the development of breast cancer after a late first full-term pregnancy. The finding that differentiation is a powerful inhibitor of cancer initiation provides a strong rationale for pursuing the identification of the genes that control this process.

Molecular biology and gynecology: CD 36 and its interactions with tamoxifen

Tamoxifen (TAM) is an antiestrogenic drug widely used in breast cancer treatment. By using the Differential Display technique in normal and malignant breast tissues, before and during TAM therapy, we were able to demonstrate that expression of the CD36 gene is down-regulated by this drug. CD36 is a cell-surface glycoprotein that acts as a receptor for thrombospondin-1, oxidized-LDL and collagens type I and IV. Thrombospondin-1 is involved in invasion, metastasis and angiogenesis and therefore the down-regulation of CD36 induced by TAM, might correspond to an alternative mechanism of action of this drug. CD36 is also one of the receptors for the oxidized-LDL which in turn is involved in pathogenesis of arteriosclerosis; thus the down-regulation of CD36 during TAM might explain the at least in part the lower levels of myocardial infarction during its use.

Nuclear phenotypical changes of human breast epithelial cells treated with carcinogens

Células epiteliais normales fueron obtenidas del tejido mamario de una paciente de 26 años en la cual se realizó una reducción mamoplástica. Las células fueron tratadas con los carcinógenos químicos N-nitro-N-metilurea (NMU), 4-nitroquinolina-N-oxido (NQO), o con 7,12-dimetil-benzantraceno (DMBA) en la fase logarítmica crescimento durante el primer pasaje en cultivo. Las células fueron analizadas a fin de detectar cambios nucleares fenotípicos tales como condensación de la cromatina, y cambios en el área nuclear. Tanto las células del grupo cocntrol como las tratadas exhibieron variaciones en condensación de la cromatina nuclear, que permitió clasificar los núcleos en dos tipos igualmente distribuidos: núcleos Tipo I, que eran pequeños, con cromatina finamente granular o filamentosa, y núcleos Tipo II, más grandes, con cromatina granular y un nucleolo prominente rodeado de cromatina condensada. Cada tipo nuclear fue subdividido en 5 subclases de acuerdo a variaciones en el área nuclear. El tratamiento con los carcinógenos cambió la frecuencia relativa de los tipos nucleares, con un aumento con los carcinógenos cambió la frecuencia relativa de los tipos nucleares, con un aumento de núcleos Tipo II y de aquéllos con mayor área nuclear. El tratamiento con NQO indujo el mayor cambio de frecuencia de núcleos Tipo I a Tipo II (del 50 al 80,5%), aumento del área nuclear y condensación de la cromatina. NMU y DMBA indujeron cambios similares, pero menos prominentes. Estos resultados permitieron concluir que el tratamiento in vitro de als células mamarias de esta paciente con carcinógenos químicos indujo cambios fenotípicos nucleares que podrían interpretarse como una expresión temprana de transformación celular maligna