Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The level of 67 kDa laminin receptor (67LR) expression on breast and colon tumor cell surfaces was previously shown to be correlated with the capacity of tumor cells to metastasize. In the present work we investigate the effects of progestins and estrogen on the expression of 67LR in two sublines of the T47D human breast cancer cells: weakly tumorigenic, poorly invasive parental T47D cells and a highly tumorigenic, more invasive T47Dco subclone. Immunoblotting with an affinity purified antibody directed against a synthetic peptide recognizes the 67LR in these cells. 67LR expression in the T47Dco subclone is 5.5-fold higher than in their parental T47D cells. Treatment of T47D cells with 1 nM of the synthetic progestin R5020 results in a 4-fold increase in 67LR protein expression. Estrogen also induced 67LR expression, but only by 1.5-fold. The progestin-stimulated expression of the 67LR correlates with a 4.3-fold increase in attachment of T47D cells to laminin. A monoclonal antibody, mAb 13, directed against beta 1 integrin, completely blocks the attachment of T47D cells to fibronectin, only partially inhibits the attachment of T47D cells to laminin, and appears not to affect the progestin-stimulated laminin attachment of T47D cells. A new antiprogestin, ZK 112.993, significantly inhibits both progestin-stimulated 67LR expression and the increased attachment to laminin. These results suggest a possible role for progestin in mediating one of the multiple events thought to be important in metastasis of steroid receptor positive human breast cancer cells.
Clin Exp Metastasis 1993 May
PMID:Expression of 67 kDa laminin receptor in human breast cancer cells: regulation by progestins. 847 97

Neonatal estrogenization of the mouse with diethylstilbestrol (DES; 2 micrograms./pup/day for days 1 to 3) or 17 beta-estradiol (200 micrograms./pup/day for days 1 to 3) resulted in epithelial dysplasia in the posterior periurethral region of the prostate at the age of 1 year. The dysplastic lesions ranged from mild to severe and, in addition to emergence of nuclear anaplasia, the architectural pattern of the glands was disturbed. Prenatal estrogenization (100 micrograms./kg. of maternal body weight on days 13 and 15 of gestation) only resulted in mild epithelial hyperplasia and occasional dysplasia in the ventral lobe of the prostate, but not in the posterior periurethral region. When neonatally estrogenized mice were allowed to grow until the age of 18 months, the degree and extent of the dysplasia of the posterior periurethral region was increased, but no frank invasion or metastases could be demonstrated. Combined estrogen and androgen treatment of neonatally estrogenized mice for 3 months (between 9 and 12 months of age) augmented nuclear dysplasia, but no invasive growth was seen in this group, either. Mild epithelial dysplasia was found in the dorsolateral lobes and coagulating glands of similarly treated control animals. A relation between the activation of certain proto-oncogenes and the development of several cancers has been shown in humans and experimental animals. In the present study, Northern blot analysis of total RNAs showed that the levels of c-myc mRNA were increased in the ventral and dorsolateral lobes, coagulating glands and prostatic urethra of neoDES mice at the age of 9 months. However, it remains to be determined whether the increase in c-myc expression is involved in the development of hyperplastic and dysplastic changes in the prostate of neoDES mice.
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PMID:Prostatic dysplasia associated with increased expression of c-myc in neonatally estrogenized mice. 850 17

Estrogen (ER) and progesterone (PR) hormone receptor status and levels were correlated with blood group antigen (A, B, H, Lewis-a and Lewis-b) expression in 48 cases of human breast cancer. Reduced expression of all the blood group antigens was observed with statistically significant reductions for H, Lewis-a and Lewis-b (P < 0.05). The proportions of ER- and PR-positive breast cancers staining for Lewis-b were greater than in hormone-receptor-negative cancers but the differences were not significant. The loss of Lewis-b antigen in breast cancer increased with tumor grade but did not correlate with axillary lymph node metastases. Loss of Lewis-b antigen is probably not a predictor of local recurrence and survival in the short period of observation. We conclude that the loss of H, Lewis-a and, especially, Lewis-b in breast cancer reflects the invasiveness of breast cancer and that Lewis-a and b expression is probably only marginally and not significantly affected by steroid hormone receptor status and levels.
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PMID:A, B, H, and Lewis-a and Lewis-b blood group antigens in human breast cancer: correlation with steroid hormone receptor and disease status. 850 39

For a majority of women with breast carcinoma, the clinical course of the disease is determined by tumor size and axillary node metastases. Tumor type and grade are also important prognostic factors. Estrogen and progesterone receptor statuses are good predictors of the likelihood of response to hormone therapy and survival. Patients with high S-phase fraction are at increased risk for early relapse. As far as other markers are concerned, sufficient information is not available currently to make definitive decisions regarding inclusion of their assessment in the routine evaluation of breast carcinomas.
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PMID:Pathology of advanced primary breast carcinoma. 853

Estrogen and progesterone receptor reactivity may be useful in identifying possible primary sites of metastatic disease or directing therapy in tumors of the female genital tract, including breast, ovary, and endometrium. Various methods have been described for the immunocytochemical evaluation of estrogen receptor (ER) and progesterone receptor (PR) status of cytologic specimens but our results have been variable. We evaluated the effectiveness of various fixatives [cytospin collection fluid, Shandon, Pittsburgh, PA (SH); ethanol (ETH); and formalin (FOR)] for fixation of smears (SM) and cell block (CB) material. The percentage and intensity of tumor nuclei of SM, CB, and tissue sections (TS) stained for ER and PR by the avidin-biotin-peroxidase complex technique were compared. Samples were considered ER or PR positive when > or = 20% of tumor nuclei were stained. The sensitivity of ER analysis of SMs and CBs in each fixative compared to formalin-fixed paraffin-embedded tissue sections were as follows: SM (SH) 88%, SM (ETH) 14%, CB (SH) 58%, CB (ETH) 43%, and CB (FOR) 70%. The sensitivity of PR determination on SMs and CBs was SM (SH) 71%, SM (ETH) 6.0%, CB (SH) 25%, CB (ETH) 33%, CB (FOR) 80%. These findings indicate that of the fixatives evaluated for ER analysis, SMs fixed in SH provided the best results. For PR evaluation, CBs fixed in FOR gave the best results.
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PMID:Expression of estrogen and progesterone receptors in cytologic specimens using various fixatives. 880 59

The development and growth of gynecological cancers are related to steroid hormone actions. Alternatively, this prompts us to study biological contribution of sex steroids for invasion and metastasis in gynecological cancers. The first step of metastasis is the detachment of tumor cells. The adherens junction forms a main cell-to-cell junctional complex, mainly consisting of E-cadherin, alpha- and beta-catenins, etc. Estrogen suppressed the expression of their mRNAs, and the adhesive function of cells via adherens junction in endometrial cancer cells. Progestin and danazol reversed the estrogen-induced suppression. Estrogen enhanced invasiveness of endometrial cancer cells though the reconstituted basement membrane and interstitium using the Boyden chamber. Progestin reduced the estrogen-induced invasiveness. The final step of metastasis is tumor-derived neovascularization for growth of metastatic cancer cells. Progestin inhibited basic fibroblast growth factor (FGF) activity, which mainly contribute to tumor-derived neovascularization, regardless of growth-inhibition in some endometrial cancers. Progestin inhibits basic FGF in well-differentiated (WD) endometrial cancer cells, but not in poorly differentiated (PD) endometrial cancer cells. TNP470, a inhibitor of vessel endothelial proliferation, inhibited directly basic FGF in the PD. Therefore, the adequate combination therapy of progestin and TNP470 could efficiently inhibit angiogenic potential of heterologous endometrial cancers. The ratio of estrogen receptor exon 5 splicing variant (ER delta E5) to wild type-ER mRNA expression increased in some metastatic lesions of cancers. The dominant expression of ER delta E5 mRNA might be related to metastatic potential of gynecological cancers. Progesterone receptor from A (PR-A), initiated from in-frame AUG present in the PR from B (PR-B) mRNA, lacks the N-terminal 164 amino acids of PR-B, and acts as a progestin-dependent, trans-dominant repressor of PR-B function and other steroid receptor function. The expression of PR-B mRNA was dominantly expressed in all metastatic gynecological cancers given. This might be related to metastatic potential of gynecological cancers. To know tumorigenic potential of sex steroid receptors, ER, PR-A and PR-B genes were transfected to NIH3T3 cells. Transfected cells with PR-A gene alone formed a few colonies in double soft agar. On the other hand, the cells with PR-B and ER genes under the presence of estradiol formed plenty of colonies. Therefore, overexpression of PR-B under the absence of PR-A might be related to tumorigenic potential. In conclusion, estrogen could enhance some steps of metastasis in endometrial cancers, and progestin could inhibit the estrogen-induced events, regardless of growth-inhibition. Relative over-expression of ER exon 5 splicing variant, and PR-B might contribute to metastatic potential in gynecological cancers.
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PMID:[Endocrinological contribution for invasion and metastasis in gynecological cancers]. 880 31

We have proposed that an early step in estrogen carcinogenesis in the hamster kidney is tubular damage followed by reparative cell proliferation. This tubular injury is progressive and increases in severity with continued estrogen treatment; one pertinent feature is a marked rise in the number of both secondary and tertiary lysosomes. Data presented herein indicate that cathepsin D, an estrogen-responsive lysosomal proteolytic enzyme, is increased in the kidney following estrogen treatment in the hamster. Three isoforms of cathepsin D were detected in estrogen-treated kidneys, 52, 31, and 27 kDa, the major being 52 kDa. At 1 and 3 months of estrogen treatment, 52-kDa cathepsin D content increased 1.4- to 1.6-fold. These changes coincided with a rise in renal estrogen receptor levels during the same estrogen treatment periods. More pronounced rises in cathepsin D levels, 2.7- and 3.5-fold, were seen after 4 and 5 months of estrogen treatment, respectively. A concomitant, 3.0- to 4.0-fold rise in estrogen receptor content was also observed. At 5 months of estradiol or DES treatment, both 27- and 31-kDa isoforms were present in hamster kidneys, in addition to the 52-kDa form. Neither progesterone nor DHT treatment affected the untreated levels of cathepsin D. Interestingly, either concomitant tamoxifen or DHT and estrogen treatment prevented the rise in cathepsin D and estrogen receptor content observed after estrogen treatment alone. Primary estrogen-induced renal tumors and their metastases exhibited markedly elevated levels of all three isoforms of cathepsin D. Immunohistochemical analysis of cathepsin D in kidney sections confirmed the Western blot findings. These data suggest a novel role for estrogen-induced cathepsin D in the hamster kidney during tumorigenesis; that is, mediating renal tubular damage as a prelude to reparative cell proliferation, thus initiating a multi-step estrogen-driven process which leads to renal tumor formation.
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PMID:Induction of cathepsin D protein during estrogen carcinogenesis: possible role in estrogen-mediated kidney tubular cell damage. 923 Feb 83

Squamous cell carcinoma in a family with dominant dystrophic epidermolysis bullosa: a molecular genetic study Squamous cell carcinoma (SCC) is a frequent complication in the severe, recessively inherited forms of dystrophic epidermolysis bullosa (RDEB), however, only rarely reported in dominant DEB. Although the SCCs in RDEB are frequently well-differentiated by histopathology, they often have a poor prognosis due to multicentricity, rapid invasiveness, and development of distant metastases. In this study, we sought to determine the molecular basis of DDEB in a family with the unusual occurrence of SCCs. Specifically, a large DDEB family with 2 individuals being affected with SCC was analyzed for potential mutations in the type VII collagen gene (COL7A1) by heteroduplex scanning and direct nucleotide sequencing of PCR amplified segments of the gene. This mutation detection strategy disclosed a G-->A transition at nucleotide position 6,235 which resulted in substitution of a glycine by arginine within the collagenous region of COL7A1. This study establishes, for the first time, the molecular basis in a family with DDEB/SCC. Clinically, this study reemphasizes the importance of vigilance in surveying DEB patients, not only those with recessive but also with dominant inheritance, for SCC.
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PMID:Squamous cell carcinoma in a family with dominant dystrophic epidermolysis bullosa: a molecular genetic study. 1023 98

Women with both a history of high grade cervical intraepithelial neoplasia (CIN III) and breast carcinoma as second primary cancer were selected for studying the presence of HPV in breast carcinomas. Paraffin embedded material from 38 patients with 41 breast carcinoma cases after CIN III were examined by polymerase chain reaction (PCR) and in situ hybridization. By PCR we detected HPV 16 DNA in 19 out of 41 cases (46%) of the breast carcinomas. One case proved to be HPV 16 positive also by in situ hybridization. HPV 16 was also detected in 32 out of the 38 patients with CIN III (84%). All HPV 16 positive breast carcinomas were HPV 16 positive in their corresponding CIN III lesions. Eight patients with diagnosed breast cancer before the CIN III lesions were used as controls. None of these had HPV positive breast carcinomas. No cases were positive for HPV 11, 18, or 33. HPV 16 was detected in the primary tumours, in local metastases from HPV 16 positive tumours, in a distant HPV 16 positive breast carcinoma metastasis to the colon, and in other primary cancers in patients with HPV 16 positive breast carcinomas and HPV 16 positive CIN III. Estrogen and progesterone receptors were quantified in the HPV positive and HPV negative breast carcinomas, and there was no significant difference in the fraction positive in the two groups. Oncogenic HPV DNA might be transported from an original site of infection to other organs by blood or lymph, and possibly be a factor in the development of cancer in different organs.
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PMID:Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). 1032 89

Mammographic screening and increased public awareness have changed the clinical spectrum of breast carcinoma with important implications for therapy. Small invasive breast carcinomas T1a,b, defined as 1.0 cm or less in maximum diameter, now comprise 22% of invasive carcinomas in our institution, enabling comparison of 273 T1a,b with 563 T1c (1.1 to 2.0 cm), 447 T2 (2.1 to 5.0 cm), and 40 T3 (>5 cm) carcinomas. Nuclear measurements were made with calibrated ocular grids. Hormone receptors were measured in cytosol or immunohistochemically. S-phase fraction (SPF) was measured prospectively on all carcinomas by counting cells in histologic preparations after vitro labeling with tritiated thymidine or 5-bromo-2'deoxyuridine. T1a (0.2 to 0.5 cm) carcinomas were similar to T1b (0.6 to 1.0 cm) in histologic and biologic features, but T1b carcinomas had higher detection rates of axillary metastasis (0% v 10%). The latter may reflect longer duration of metastases, permitting growth to detectable size. Low-grade carcinoma types (mucinous, tubular, cribriform) became less frequent as T stage increased, with the major decrease occurring at T1b (0.6 to 1.0 cm)/T1c (1.1 to 2.0 cm) boundary. T1a,b carcinomas preponderantly had low-grade histologic and biochemical characteristics and low SPF. SPF increased significantly with increasing tumor size from T1b through T2 but not beyond T2. Increases in proportion of patients with axillary metastases occurred over each T transition. Estrogen and progesterone receptor (ER, PgR) positivity decreased with increasing stage. Larger tumors were significantly associated with younger patient age. While this may reflect ease of diagnosing small carcinomas after the menopause, young age was also associated with predictors of aggressive tumor behavior (high SPF, negative assays for ER, PgR). T1a,b patients with mid or high SPF or axillary metastases were more likely than others to have received cytotoxic adjuvant therapy. Conclusions are: (1) Development of cell lines that have metastatic capability appears to occur near the T1b/T1c interface, but they exist very early in some carcinomas. (2) T1a carcinomas may be managed without axillary dissection. When T1b patients are candidates for adjuvant therapy, we advocate sentinel node biopsy with intensive study for micrometastases. (3) Accurate determination of size is very important in prognosis of small breast carcinomas. (4) Prognostic efficacy of proliferation and other prognostic markers in retrospective studies, but not in our patients who often received adjuvant therapy, suggest that micrometastases from small breast carcinomas are highly responsive to adjuvant chemo/hormonal therapy.
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PMID:Pathology and behavior of small breast carcinomas. 1049 Feb 2


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