Differentiation of the mammary gland and susceptibility to carcinogenesis

  title={Differentiation of the mammary gland and susceptibility to carcinogenesis},
  author={Jos{\'e} Russo and Lee K. Tay and Irma H. Russo},
  journal={Breast Cancer Research and Treatment},
SummaryIt has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7, 12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen… 

Relationship between histology, development and tumorigenesis of mammary gland in female rat

The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.

Characterization of Breast Cancer Progression in the Rat

The DMBA‐treated rats provide a useful model to dissect the early changes that occur during the multistep process of mammary gland carcinogenesis, including an initial decrease followed by a gradual increase in the labeling index of PCNA.

Influence of Normal Mammary Epithelium on Breast Cancer Progression: The Protective Role of Early Pregnancy

Results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice, mainly through an extrinsic pathway.

The Genomic Basis of Breast Development and Differentiation

The degree of differentiation acquired through early pregnancy has changed the genomic signature that differentiates the lobule type 1 in the early parous women from that in the nulliparous women, making this the postulated mechanism of protection conferred by early full-term pregnancy.

Primary prevention of breast cancer by hormone-induced differentiation.

  • I. RussoJ. Russo
  • Biology, Medicine
    Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
  • 2007
The data indicate that hCG, like pregnancy, induces permanent genomic changes that are not reproduced by steroid hormones and in addition regulates gene expression through epigenetic mechanisms that are differentiation-dependent processes, leading to conclude that hormonally induced differentiation offers enormous promise for the primary prevention of breast cancer.

The concept of stem cell in the mammary gland and its implication in morphogenesis, cancer and prevention.

Evidence is provided that pregnancy, through the process of cell differentiation, shifts the Stem cell 1 to Stemcell 2, cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis.

Molecular basis of pregnancy-induced breast cancer protection

  • J. RussoG. Balogh I. Russo
  • Biology
    European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation
  • 2006
Evidence is shown that the breast tissue of post menopausal parous women has had a shifting of stem cell 1 to stem cell 2 with a genomic signature different from similar structures derived from postmenopausal nulliparous women that have stem cell1.

Hormone prevention of mammary carcinogenesis by norethynodrel-mestranol

It was concluded that treatment of virgin rats with the hormone combination norethynodrel-mestranol resulted in long lasting structural changes in the mammary gland which protected this organ from a subsequent carcinogenic insult.

Atlas and Histologic Classification of Tumors of the Rat Mammary Gland

This work attempts to provide a working framework for diagnosis of the type of lesions found in the mammary glands of rats treated with chemical carcinogens or radiation and to clarify criteria for establishing the basic biological characteristics of tumors.

Role of Hormones in Mammary Cancer Initiation and Progression

  • I. RussoJ. Russo
  • Biology, Medicine
    Journal of Mammary Gland Biology and Neoplasia
  • 2004
It is still unclear whether estrogens arecarcinogenicity of estrogens to the human breast, but in experimental animal models estrogens can induce mammary cancer.



Susceptibility of the mammary gland to carcinogenesis: I Differentiation of the mammary gland as determinant of tumor incidence and type of lesion.

The influence of age and mammary gland differentiation on the incidence of tumors induced by 7,12-dimethylbenz(a)anthracene (DMBA) was studied by correlating the development of the mammary glands of

Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence.

While pregnancy and lactation protected the mammary gland from developing carcinomas and benign lesions by induction of full differentiation, pregnancy interruption did not elicit sufficient differentiation in the gland to be protective, and these animals were at the same risk as virgin animals treated with the carcinogen.

Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland to carcinogenesis.

The results suggest that the high susceptibility to carcinogenesis that has been demonstrated in young virgin rats is due to the presence of a large proliferative compartment, mainly in terminal end buds and TD, while the low susceptibility of parous animals isDue to the formation of alarge compartment of nonproliferating cells, and that those cells still proliferating have a longer G1 than do those of young and old virgin rats.

Mammary carcinogenesis by 3-methylcholanthrene. I. Hormonal aspects in tumor induction and growth.

The failure to induce mammary cancer in males suggests that estrogens are important in mammary carcinogenesis induced by 3-methylcholanthrene, and increased progesterone stimulation seemed to be a factor in the rapid induction of tumors during pregnancy.

Influence of age and parity on the susceptibility of rat mammary gland epithelial cells in primary cultures to 7,12-dimethylbenz(a) anthracene

It is indicated that age and parity influence the proliferative status of the cells and their susceptibility to DMBA in vitro, simulating in that way the in vivo situation.

Endocrine influences on human mammary cancer formation a critique

Stress, tissue anoxia, ACTH therapy, pregnancy, hypothyroidism, obesity, castration and menopause normally increase the rate of estriol excretion relative to other estrogens and must be considered in future investigations needed to elucidate the divergent results reported for C18 steroid excretion in this disease.


Hypophysectomy was the most effective method found to induce regression of mammary cancer in the present experiments.

Relationship between previous reproductive history and chemically induced mammary cancer in rats

  • R. Moon
  • Biology
    International journal of cancer
  • 1969
The relationship between party and carcinogen‐induced mammary cancer in the rat is similar to that existing in the human female but opposite to that found for the mouse.

The role of the adrenal cortex in mammary development and its relation to the mammogenic action of the anterior pituitary.

It has been shown that desoxycorticosterone will evoke growth of the mammary alveolar tissue in the monkey, mouse, mouse and guinea pig, while Nelson has observed mammary development in hypophysectomized-gonadectomized rats treated with adrenotrophin.

Causes of age-dependency of mammary tumour induction by carcinogens in rats.

  • H. Nagasawa
  • Medicine
    Biomedicine / [publiee pour l'A.A.I.C.I.G.]
  • 1981
The mechanism of well-known protection by early pregnancy and lactation of human breast cancer and the possibility for prophylaxis of breast cancer were discussed.