This book will provide the latest advances in molecular and cellular biology for establishing the foundation of a complete understanding of the mechanisms of breast differentiation leading to cancer prevention. The authors are based on the epidemiological evidence indicating that early first full term pregnancy is a protective factor in human against breast cancer and they have used this paradigm and developed experimental systems in both in vivo and in vitro that have demonstrated mechanistically how the differentiation at the organ and cellular level takes place. This knowledge has provided the blueprint for developing better understanding of the basis of cancer prevention. The transcriptoma analysis of the breast of pre and post-menopausal women has established a genomic signature imprinted in the breast that differs according to the reproductive history of the woman showing that early first full term pregnancy reprogram the organ. This reprogramming takes place at the chromatin level by changing the transcriptional process. The modification of the transcriptional control is due to the expression of non coding RNA sequences and posttranscriptional control driven by the splicesome. The plasticity of the genome of the human breast make possible this reprogramming that is not only induced by the physiological process of pregnancy but by the use of hormones that mimic pregnancy without pregnancy. The author have established the basis of clinical trials for prevention and the discovery that short 15aa peptides of the chorionic gonadotropin hormone can be used in human breast cancer prevention based on preclinical and clinical data.
Provides new insight on cancer prevention based on meticulously researched processed that have been gleaned from basic to translational research with a direct clinical application
Targeted to the medical profession and those interested in biomedical research
Outlines a model to the basic researchers and for those that are aiming to apply their work in the future to the clinic
This book is designed for advanced students and researchers in cell biology, biochemistry, molecular biology, medicine in general, and cancer in particular. It provides the latest data on the transcriptome of the mammary gland in order to establish the molecular and cellular biology of differentiation leading to cancer prevention. The authors have based their work on the epidemiological evidence that early first full term pregnancy is a protective factor in humans against breast cancer and using this knowledge have developed in vivo and in vitro experimental systems that have demonstrated mechanistically how the differentiation takes place. The transcriptoma analysis of the female breast shows that an early first full term pregnancy reprograms the organ by imprinting a genomic signature that differs according to reproductive history. This reprogramming takes place at the chromatin level by changing the transcriptional process. The modification of the transcriptional control is due to the expression of non-coding RNA sequences and post-transcriptional control driven by the spliceosome. The plasticity of the genome of the human breast makes possible this reprogramming that is not only induced by the physiological process of pregnancy but by the use of hormones mimicking pregnancy. The role of stem cells and their reprogramming during differentiation are presented as a new paradigm in breast cancer prevention.
Preface.- The epidemiology of breast cancer and the basis for prevention.- In vivo model for breast cancer prevention.- Comparative effects of the preventive effect of pregnancy, steroidal hormones and hCG in the transcriptomic profile of the rat mammary gland.- The use of in vitro three-dimensional system for testing preventing agents.- Methodological approach fro studying the human breast.- The transcriptoma of breast cancer prevention.- Chromatin remodeling and pregnancy induced differentiation.- The role of spliceosome in the human breast.- Non coding RNAs and breast cancer prevention.- The role of stem cell in breast cancer prevention.- Index.