RETROVIRUSES IN BREAST CANCER: A CHALLENGE FOR FUTURE RESEARCH
Iafa Keydar, Ph.D.,Dept. of Cell Research and Immunology, Tel Aviv, Israel.
Abstract
Since the discovery of the mouse mammary tumor retroviruses (MMTV) by Bittner, and their involvement in mammary adenocarcinoma in mice, scientists have proposed a similar model in human breast neoplasia. Several lines of research supported the participation of a MMTV-like virus in the human disease. During the years contradictory results have been published. The human genome contains a large number of endogenous retroviral sequences (HERV) closely related to infectious retroviruses acquired 10 million years ago and constitute 0.1% of our germ line. some studies report that also most HERVs are defective, some of them containing functional long terminal reports and long open reading frames for Gag, Pol and Env proteins. The latest publications showing that 38% of human breast tumors contain sequences 90-98% homologous to MMTV, Env and LTR support our and other researchers’ data of a MMTV-like endogenous virus in human breast cancer. A hypothetical model of such a virus is presented.
(Women and Cancer, Vol. 1 Number 1:1-7,1998)
HORMONALLY ACTIVE ENVIRONMENTAL EXPOSURES AND THEIR RELATIONSHIP TO RISK FOR REPRODUCTIVE CANCER AMONG WOMEN
Mary S. Wolff; Ph.D., Gertrud S. Bcrkowitz, Ph.D., Steven Brorver, M.D., Joel Forman, M.D., James Godbold, Ph.D., Nathan Kase, M.D., Robert Lapinsti, Ph.D., Signe Larson, M.D., Ruby Senie, Ph.D., Paul Tartter, M.D.
Department of Community and Preventive Medicine, Mount Sinai School of Medicine, Box 1057, 1 Gustave L. Levy Place, NewYork, NY 10029
Abstract:
Risk for cancer of the reproductive organs among women varies widely in different ethnic, geographic and migrant groups. Much of the variability in cancer incidence may be explained by contrasting dietary patterns as well as environmental exposures in diverse populations. Knowledge about exposures among racial/ethnic groups and about hormonal effects of such exposures can enhance our understanding of the etiology of breast, uterine and ovarian cancers that are strongly, though not identically, associated with reproductive landmarks such as age at menarche and parity. Phytoestrogens and organochlorine exposures, as examples, vary widely with ethnicity in a pattern that may influence cancer risk. Limited evidence suggests decreased risk for breast or uterine cancer associated with higher intake of phytoestrogens. A review of previous research and preliminary data are presented in this paper which show wide variability in diet of phytoestrogens among racial/ethnic groups of American women. In preliminary data collected in 1993-1995, we also found higher organochlorine exposures among African-Americans and Hispanics compared with Caucasians in New York City. Hormones and xenobiotics can alter onset of puberty, and age at menarche, risk factors for breast and uterine cancer. Such, exposures may explain the fact that African-American girls experience onset of puberty and menarche at a younger age than Caucasian girls do; in the United States. Preliminary data on puberty stage, of 110 girls are presented that indicate that Hispanic girls are intermediate between these two racial/ethnic groups, while their breast cancer risk is low, consistent with a modulating effect of diet upon obesity among Hispanic women. Preliminary data represented on dietary intake of phyto-estrogen-containing foods, which are hypothesized to delay puberty through their anti-estrogenic activity. Nine year old Hispanic girls (n=22) reported significantly higher intake of foods with phytoestrogen content above 15 ug/day than African American (n=18) and Caucasian girls (n=24).
Environmental and dietary exposures may act alone or in comminations with other risk factors to influence reproductive function throughout life and to support or repress tumor growth. Detrimental exposures are potentially preventable and protective exposures can be enhanced. Therefore identification of these risks is an important goal for future research.
(Women and Cancer, Vol. 1 Number 1:8-20, 1998)
GROWTH FACTORS AND THEIR RECEPTORS: A NOVEL APPROACH TO THE ENDOCRINOLOGY OF HUMAN BREAST CANCER
William J. Gullick, Ph.D.,1 Caterina Bianco, M.D.S, Nicola Normanno, M.D.2 Isabel Martinez-Lacaci, Ph.D., Marta De Santis, Ph.D., Andreas D. Ebert, M.D., Ph.D.3, David S. Salomon, Ph.D.,
1
ICRF Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Hospital, London W12, ONN, England; 2. Oncologia Sperimentale D, Istituto, Nazionale per lo Studio e la Cura, Dei, Tumori-Fundazione Pascale, 80131, Naples, Italy; 3Dept. of Obstetrics and Gynecology, Medical School Benjamin Franklin, Free University Berlin, 12200, Berlin, Germany
Abstract
Breast cancer represents a prevalent malignancy in women of western countries. The therapies that are routinely used to treat breast cancer patients were developed several decades ago and include surgery and radiation to control local disease with or without chemotherapy and hormonal therapy to eliminate metastatic disease. Failure to achieve a complete eradication of the tumor in most patients is primarily due to acquired resistance to drug and/or hormonal therapy. In addition, chemotherapeutic agents act by killing rapidly proliferating cells without exhibiting any degree of selectivity for malignant cells, thereby presenting a high degree of toxicity to the patient. For these reasons, there has been an increasing effort to better understand the biology of this disease and to translate these advances in biological knowledge into improvements in diagnosis and therapy. A promising area for the application of novel diagnostic, prognostic and therapeutic approaches involves growth factors and their receptors. Several studies have demonstrated that breast cancer cells synthesize and respond to different families of growth factors and overexpress specific receptors which can function in a cooperative fashion; to modulate tumor growth, angiogenesis and metastasis. (Women and Cancer, Vol. 1 Number 1:29-57, 1998)
NEW GENOMIC MARKERS IN THE PROGRESSION OF BREAST CANCER
Keltouma Driouch, Ph.D and Rosette Liderau, D.Sc., Laboratoire d’Oncogentique, Centre Rene Huguenin, 35 rue Dailly, F-92211,St-Cloud, France
Abstract
Breast tumorigenesis and metastasis result from an accumulation of genetic alterations involving "cancer genes". In human cancers, these alterations have mostly been studied in primary tumors. The main recurrent genetic abnormalities observed in primary breast tumors are amplification of proto-oncogenes (MYC, ERBB2, CCND1), mutations of TP53, and loss of heterozygosity (LOH) on chromosomes and chromosome arms 1, 3p, 6q, 7q, 8p, 9p, 11, 13q, 16q, 17, 18q, and 22q. The prognostic value of these genetic alterations have been greatly investigated and some of them have been related to a poor prognosis, i.e., progression of the disease (decreased survival, early relapses, etc.). However, it is not clear yet whether specific chromosome regions are directly associated to the metastatic process owing to a lack of screening studies for genetic alterations in secondary events. Genes probably involved in the metastatic process have mainly been investigated in experimental bioassay systems. In these models, putative metastasis-related genes have been identified, such as NME1 (17q), CDH1 (16q), TSG101 (11p), and KISS1 (1q). Moreover, LOH analyses have defined regions of deletion associated with metastasis on several chromosomal regions (3p21.3, 15q14, and 16q22.2-23.2). These studies of genetic alterations associated to tumor progression could lead to the characterization of new genomic markers of tumors aggressiveness and enhance our understanding of the molecular mechanisms of metastasis and cancer progression. (Women and Cancer, Vol. 1 Number 1:58-81,1998)
RAPID, NONGENOMIC ACTIONS OF ESTROGENS
Cheryl S. Watson, Bahiru Gametchu+, Andrea M. Norfleet, Celeste H. Campbell, and Mary L. Thomas*
Department of Human Biological Chemistry and Genetics and *Pharmacology and Toxicology, University of Texas Medical Branch, Galveston TX 77555, +Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226
Abstract:
Membrane-initiated or nongenomic activities of estrogens contribute to the effects of estrogen on a wide variety of classical female reproductive tissues as well as nonreproductive and male tissues. Membrane-initiated responses are discussed in terms of their preparative functions supporting subsequent genomic responses leading to tissue or tumor growth. Functional consequences of membrane-initiated estrogenic actions in nonreproductive or male tissues are proposed. The wide variation in signal transduction schemes employed by various tissues is summarized and discussed in terms of the identity of proteins that mediate these responses. Probable mixed binding systems for steroids in plasma membranes are compared to similar multiple hormone binding protein systems in extracellular fluids and inside cells. These issues are related to estrogen-induced tumor growth, the actions of environmental estrogens, and the integration of membrane-initiated effects with genomic mechanisms.
(Women and Cancer, Vol. 1 Number 1:21-28, 1998)
