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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three topics are briefly reviewed relating to carcinogenesis of estrogen responsive tissues: (a) enzymology of benzo(a)pyrene activation by human tissues, (b) microsomal activation of estrogens to estrogen arene oxides and (c) estrogen and progesterone receptor studies in endometrial carcinoma. The following working hypothesis is stated on the etiology of gynecologic tumors: "Environmental chemicals, such as cigarette smoke, polycyclic and polyhalogenated hydrocarbons, etc., induce special forms of cytochrome P-450 monooxygenase and related enzyme systems which can activate endogenous or prescribed estrogens and non-steroid antiestrogens to act as initiators and/or promoters of neoplasia in estrogen-dependent organs." The role of estrogen receptors is perceived as a homing device or cellular "Trojan Horse" for these activated estrogens.
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PMID:Carcinogen activation by human uterine enzymes. 46 42

Rat mammary carcinomas were induced by directly inserting activated neu or ras genes into in situ rat mammary ductal cells using replication-defective retroviral vectors. neu was over 200 times more potent than ras in inducing rat mammary carcinomas. Ovariectomy 2 days postinfection dramatically reduced the occurrence of carcinomas induced by neu and extended their latency. In general, early ovariectomy had much less effect on the occurrence of carcinomas induced by ras and had no significant effect on their latency. Carcinomas induced by neu in ovariectomized rats had down-regulated estrogen receptor and progesterone receptor, while those induced by ras had only down-regulated progesterone receptor. Fully progressed mammary carcinomas in intact rats induced by both neu and ras had a similar response to ovariectomy, with an approximate regression rate of 60%. These data suggest that the activation of ras, but not neu, can replace at least some functions performed by ovarian hormones in the early phases of mammary carcinogenesis. These data also suggest a role for antiestrogen drug therapy in the prevention of neu-associated breast cancer.
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PMID:Difference in the response of neu and ras oncogene-induced rat mammary carcinomas to early and late ovariectomy. 135 10

Inbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone-dependent endometrial adenocarcinoma. Here we characterize the RUCA-I cell line derived from an endometrial adenocarcinoma of an inbred DA/Han rat and the RUCA-II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA-I cell line, if transplanted to the neck of female DA/Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub-class. In contrast, ectopic tumor growth of the RUCA-II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA-I and RUCA-II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA-binding state. In contrast, the rate of proliferation of RUCA-I but not of RUCA-II cells was reduced in the presence of 10(-6) M tamoxifen. From these results we conclude that (i) both cell lines, RUCA-I and RUCA-II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone-dependent growth regulation of RUCA-I and RUCA-II cells is obviously impaired; (iii) the RUCA-I cell line appears to be a suitable model system for the study of molecular aspects of estrogen- and tamoxifen-dependent gene expression.
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PMID:Functions of estrogens and anti-estrogens in the rat endometrial adenocarcinoma cell lines RUCA-I and RUCA-II. 145 35

This review of the action of estrogens and progestagens, the steroids in oral contraceptives, on cells in the endometrium, breast, ovary, cervix and other tissues, regarding possible causative role in cancer development focuses on the level of steroid receptors and observed actions of these hormones on the cellular level. The steroid hormones are thought to interact with cells by binding to a specific receptor on the cell surface, especially estrogen receptors, while progestagen receptors overlap with glucocorticoids and androgens. Oral contraceptives typically have progestin dosages at the plateau of the dose-response curve, but lower estrogen doses may possible improve the cancer risk. Plasma levels are not reliable estimates of estrogen influence; moreover, estrogens are synthesized locally. Carcinogenesis is a multi-stage process requiring cell proliferation, involving an initiating event, and probably promotion agents, resulting in tumor growth. Estrogens increase cell replication in endometrium, and progestins counter it. Breast cancer evolves in several cell types in the epithelium of the terminal ductal lobular unit, with a 20-year latency. Estrogens stimulate ductal growth and progestins its development, and both are required for full stimulation, as in pregnancy. Estrogens usually stimulate cancer growth, but the precise sensitivity to steroids depends on the timing in the life cycle of the tumor. Ovarian cancer is unique in that neoplasms arise from the epithelium, not the hormone-sensitive tissue. Therefore the suppressive effect of steroids on ovarian neoplasia is thought to be via down- regulation of the gonadotropins, prevention of follicular rupture and consequent cell division of the epithelium, or some effect on growth regulating factors. The effect of steroids on the cervix is unclear, since cervical cancers are hormone-resistant, but there may be a step in transformation by human papilloma virus that involves a glucocorticoid- or progesterone receptor. Steroid receptors are also known to exist in tumors of liver, skin, colon, kidney and anterior pituitary, but their function is neoplasia is unknown.
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PMID:Biology of female sex hormone action in relation to contraceptive agents and neoplasia. 165 Dec 4

We analyzed the alteration of the hst-1 and int-2 genes in 36 cases of esophageal squamous cell carcinoma, 42 cases of gastric adenocarcinoma, and 52 cases of colorectal adenocarcinoma. Coamplification of the hst-1 and int-2 genes was observed in 19 of 36 esophageal carcinomas (52%), 16 of 34 primary tumor tissues (47%), and 10 of 10 metastatic tumors (100%). The degree of amplification ranged from 4- to 8-fold. The incidence of hst-1 and int-2 gene coamplification was significantly higher in male patients than that in female patients (P less than 0.05). The coamplification of the hst-1 and int-2 genes had a tendency to correlate with clinical stage. The progesterone receptor gene, which is mapped to chromosome 11 at band q21-23, was not amplified in these esophageal carcinomas. Coamplification of the hst-1 and int-2 gene does not seem to imply increased numbers of chromosome 11, and the hst-1 and int-2 genes appear to be in same amplification unit on chromosome 11 at band q13. No coamplification of the hst-1 and int-2 genes was detected in gastric carcinomas and colorectal carcinomas. These results suggest that amplification of chromosomal locus of the hst-1 and int-2 genes might participate in carcinogenesis, in progression, and particularly in metastasis of esophageal carcinomas.
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PMID:High incidence of coamplification of hst-1 and int-2 genes in human esophageal carcinomas. 252 25

In most target cells of the female genital tract, adequate cell differentiation is obtained via the successive and synergistic actions of estradiol (E2) and progesterone (P). This mainly due to the fact that progesterone receptor (PR) synthesis involves the prior action of estradiol through its receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas lobular development depends on progesterone secretion. In other words E2 + P, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. On the other hand progesterone may also have an antagonistic action against E2. The antiestrogen activity of progesterone is mediated through a decrease in the replenishment of E2 receptor and the synthesis of 17 beta-hydroxysteroid dehydrogenase, which leads to an accelerated metabolism of E2 to E1 in the target organ itself. These biochemical events, which have been well documented in the endometrium, have also been shown in cultures of normal breast epithelial cells as well as in differentiated fibroadenomas with high cellular density. In addition, data from the literature show that E2 added to human breast cells increases cell multiplication by means, eventually, of the synthesis of growth factors. Progesterone and progestins have a reverse effect. Data from our laboratory indicate that in normal cultured cells E2 and progestins are also antagonists with regard to cell multiplication. From these different data, it is postulated that in human beings, long periods of a luteal-phase defect leading to an unopposed estrogen effect might be a promoter of carcinogenesis in the breast.
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PMID:Estradiol/progesterone interaction in normal and pathologic breast cells. 352 47

Previous studies on the cell-cell adhesion molecules P- and E-cadherin have shown that P-cadherin is not expressed in breast cancer. In contrast, the expression of E-cadherin is a normal event in these tumors, but a reduction in the levels of this molecule in neoplastic cells is associated with the histological type, high histological grade, greater tumor size, and metastasis. The expression pattern of P- and E-cadherin were immunohistochemically studied in tissue sections from normal breast tissue, benign breast lesions, and 57 infiltrating breast carcinomas. Cadherin expression was analyzed in parallel with pathological features and the immunohistochemical expression of estrogen and progesterone receptors in breast carcinomas. P-cadherin was detected in the myoepithelial cells and E-cadherin in luminal epithelial cells from normal breast and benign breast lesions. P-cadherin expression was detected in 9 of 45 cases (20%) of infiltrating ductal carcinomas of no special type; none of the special histological types that were analyzed (7 infiltrating lobular carcinomas, 3 colloid carcinomas, and 2 infiltrating papillary carcinomas) expressed P-cadherin. In infiltrating ductal carcinomas, P-cadherin expression correlated significantly with a reduction in E-cadherin expression, histological grade (all cases were grade III tumors), and hormone receptor content (8 of 9 cases were estrogen and progesterone receptor negative). Although E-cadherin was not found in the 7 infiltrating lobular carcinomas, it was present in the remaining histological types and was preserved in 15 infiltrating ductal and 3 colloid and 2 papillary carcinomas and was reduced in 30 infiltrating ductal carcinomas. In addition, a reduction in E-cadherin expression was significantly associated with high histological grade and a lack of steroid hormone receptors in infiltrating ductal carcinomas. No apparent relationship was found between P- and E-cadherin expression and tumor size and axillary lymph node metastasis. The distinct patterns of P- and E-cadherin expression observed in this study strongly suggest a differential role for these cadherins in human breast carcinogenesis.
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PMID:Anomalous expression of P-cadherin in breast carcinoma. Correlation with E-cadherin expression and pathological features. 753 41

Allele imbalance on chromosome 11 loci in ovarian cancer is a frequent event, suggesting the presence of tumour-suppressor genes for ovarian carcinogenesis on this chromosome. Ten highly polymorphic (CA) repeat microsatellites were used to determine allele imbalance in 60 primary ovarian tumours, including 47 epithelial ovarian cancers (EOCs). Forty EOCs (85%) showed allele imbalance at one or more loci, and in 39 of these (83%) the data suggested subchromosomal deletions: eight of 11p only; six of 11q only; and 25 of both 11p and 11q. Three consensus regions of deletion were indicated at 11p15.5-p15.3, 11q12-q22 and 11q23.3-q24.1. Allele imbalance at the 11q subtelomeric region (D11S912) correlated significantly with adverse survival, while imbalance at 11q14.3 and retention of heterozygosity at 11q22 (close to the site of the progesterone receptor gene) were associated with favourable clinicopathological features. The findings allow development of a preliminary model for the molecular evolution of epithelial ovarian cancer.
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PMID:Chromosome 11 allele imbalance and clinicopathological correlates in ovarian tumours. 764 Feb 20

A moderately-differentiated endometrial adenocarcinoma cell line(EI) was established from a surgical specimens obtained from a 55-year-old woman with endometrial carcinoma. This cell line could be transplanted to nude mice, where the cells showed the same histological type as the primary tumor. The doubling time of the cell line was 50.5 hours; the saturation density was 7.5 x 104 cells/cm2; the plating efficiency was 46%. This cell line was determined to produce TPA, but not other tumor markers, such as CA125 or CEA. Neither estrogen receptor, nor progesterone receptor was detected from the culture cell or the primary tumor. Chromosome analysis revealed that cells examined were all 46,XX, + 8,t(14q14q), and only cells with this karyotype were thought to be able to grow. From these results, it was suggested that a gene on No. 8 chromosome would be involved in the carcinogenesis of endometrial adenocarcinoma. Thus this cell line was thought to be useful for the clarification of gene conversion during the process of development of endometrial adenocarcinoma.
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PMID:[Establishment and characterization of the new cell line (EI) from a human endometrial adenocarcinoma]. 766 52

The topographical distribution of oestrogen and progesterone receptors in the human endometrium and Fallopian tube was investigated by an immunocytochemical technique. A gradient of positively stained cells was observed: the highest oestrogen and progesterone receptor content was noted in the fundal part of the uterine cavity and the ampullar region of the Fallopian tube. The observed gradient is in keeping with biological and pathological events that occur in the human mullerian tract, e.g. fecundation, implantation and carcinogenesis.
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PMID:Topographical distribution of oestrogen and progesterone receptors in the human endometrium and fallopian tube. An immunocytochemical study. 768 10


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