Cables1 is a tumor suppressor gene that regulates intestinal tumor progression in Apc(Min) mice.

The transformation of colonic mucosal epithelium to adenocarcinoma requires progressive oncogene activation and tumor suppressor gene inactivation. Loss of chromosome 18q is common in colon cancer but not in precancerous adenomas. A few candidate tumor suppressor genes have been identified in this region, including CABLES1 at 18q11.

TIP30 is associated with progression and metastasis of prostate cancer.

Tat-interacting protein 30 (TIP30), a transcriptional repressor for ERalpha-mediated transcription, possesses several characteristics of a tumor suppressor in certain human and mouse cells. It is reported that deletion of TIP30 gene preferentially increases tumorigenesis in the female knockout mice. Here, we analyzed TIP30 gene expression in the databases of several DNA microarray studies of human prostate cancer and show that TIP30 is specifically overexpressed in metastatic prostate cancers.

Mechanisms of Cables 1 gene inactivation in human ovarian cancer development.

Cables 1, a cyclin-dependent kinase binding protein, is primarily involved in cell cycle regulation. Loss of nuclear Cables 1 expression is observed in human colon, lung and endometrial cancers. We previously reported that loss of nuclear Cables 1 expression was also observed with high frequency in a limited sample set of human ovarian carcinomas, although the mechanisms underlying loss of nuclear Cables 1 expression remained unknown.

The Cables gene on chromosome 18q is silenced by promoter hypermethylation and allelic loss in human colorectal cancer.

Cables is a cyclin-dependent kinase-binding nuclear protein that maps to chromosome 18q11-12. Here, we assessed Cables expression in 160 colorectal cancers (CRCs), its role in colon cancer cell growth, and the potential mechanisms of Cables inactivation. Expression levels, promoter methylation, and mutational status of Cables were investigated in colon cancer cell lines and primary colon tumors.

The Cables gene on chromosome 18Q regulates colon cancer progression in vivo.

Early events involved in the pathogenesis of colorectal cancer include mutations in the Adenomatous Polyposis Coli tumor-suppressor gene and oncogenic KRAS mutations. Later events include deletions on chromosome 18q, which are observed in a high proportion of colorectal cancers. However, the important tumor suppressor genes targeted by these deletions have not been fully defined.

Aberrant splicing of cables gene, a CDK regulator, in human cancers.

Cables is a novel cell cycle regulatory protein that interacts with cdk2, cdk3, and cdk5. Cables inhibits cdk2 activity by enhancing cdk2 tyrosine 15 phosphorylation by Wee1, which consequently leads to inhibition of cell growth. Loss of Cables expression was found in many human cancers, especially colon and endometrial cancer.

Increased growth rate, delayed senescense and decreased serum dependence characterize cables-deficient cells.

Cables (Cables1), a recently described growth suppressor protein that maps to human chromosome 18q11-12, is lost in many primary colon, lung, and gynecological malignancies. Cultured cell lines that overexpress Cables show a reduction in cell proliferation and Cables(-/-) mice are viable with normal embryonic development. Since Cables expression is lost in primary human tumors and overexpression of Cables suggests a role in growth suppression, we investigated growth properties of primary mouse embryonic fibroblasts (MEFs) from Cables(-/-) and Cables(+/+) mice.

Defining the extent of cables loss in endometrial cancer subtypes and its effectiveness as an inhibitor of cell proliferation in malignant endometrial cells in vitro and in vivo.

Loss of Cables expression is associated with a high incidence of endometrial hyperplasia and endometrial adenocarcinoma in humans. The Cables mutant mouse develops endometrial hyperplasia and following exposure to chronic estrogen develops early endometrial adenocarcinoma. The objectives of the current study were to determine if: (1) loss of Cables expression occurred in high grade endometrioid adenocarcinoma, uterine serous and clear cell carcinoma as observed in endometrial hyperplasia and low grade endometrial adenocarcinoma; (2) overexpression of Cables inhibited cell proliferation in endometrial cancer (EC) cells in vitro and in vivo; and (3) progesterone could regulate the expression of Cables mRNA.

Studies on the differentiation pathway and growth characteristics of epithelial culture cells of the human prostate.

We established explant primary cultures in order to study the growth and hormone responsiveness, and the differentiation process of prostatic epithelial cells. Cell outgrowth was achieved from explant tissue by using a new DU145-cell-conditioned medium and special plastic coverslips. To define the present model, proliferation assays were tested by [3H]thymidine assay and planimetric analysis.

Effect of keratinocyte growth factor and activin on cell growth in the human prostatic cancer cell line LNCaP.

Keratinocyte growth factor (KGF) has paracrine properties in the human prostate which stimulate epithelial cell growth. Activins have profound effects on cell growth and function in the human prostate, and are expressed in LNCaP, DU 145 and PC3 cells. LNCaP cells were characterized by immuncytochemistry, an immunoassay and polymerase chain reaction.

Loss of cables, a cyclin-dependent kinase regulatory protein, is associated with the development of endometrial hyperplasia and endometrial cancer.

Endometrial cancer is the most common gynecological cancer in Western industrialized countries. Cables, a cyclin-dependent kinase binding protein, plays a role in proliferation and/or differentiation. Cables mutant mice are viable, but develop endometrial hyperplasia and carcinoma in situ at a young age.

Loss of cables, a novel gene on chromosome 18q, in ovarian cancer.

Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11. Cables appears to be primarily involved in cell cycle regulation and cell proliferation. Overexpression of Cables in Hela and other cell lines inhibits cell proliferation and tumor formation.

Loss of cables protein expression in human non-small cell lung cancer: a tissue microarray study.

Loss of heterozygosity (LOH) on chromosome 18q is common in lung cancer. The genes involved in LOH on 18q in lung cancer have not been well characterized. Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11-12.

Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.

Cyclin-dependent kinase 2 (cdk2) is a small serine/threonine kinase that regulates cell cycle progression. Cdk2 activity is tightly controlled by several mechanisms, including phosphorylation and dephosphorylation events. Cables is a recently described novel cdk-interacting protein.

Regulation of keratinocyte growth factor receptor and androgen receptor in epithelial cells of the human prostate.

Purpose: Stromal-epithelial interactions of growth factors and the androgen receptor may have implications for the pathophysiology of benign and neoplastic transformation of the human adult prostate. We investigated a possible interaction of keratinocyte growth factor with its receptor as well as with the androgen receptor signaling pathway in human prostatic epithelial cells.

Materials And Methods: Human prostatic epithelial cells were obtained from explant primary culture, established in DU145 cell conditioned medium and maintained in keratinocyte serum-free medium with supplements.

Immunolocalization of the keratinocyte growth factor in benign and neoplastic human prostate and its relation to androgen receptor.

Background: Growth and development of the prostate are androgen-dependent. Keratinocyte growth factor (KGF), widely expressed by mesenchymal cells, is thought to act like an andromedin between stroma and epithelium of the prostate. Since KGF has recently emerged as an autocrine mediator in prostate cancer, we investigated the role KGF plays in the human prostate and its relationship to androgen receptor (AR).

Characterization of a stromal cell model of the human benign and malignant prostate from explant culture.

Purpose: There is a lack of suitable in vitro models for the human prostate. To study stromal-epithelial interactions, we established stromal cells in cultures from benign and malignant prostate tissue that resemble more closely the in vivo conditions of the human prostate.

Materials And Methods: Stromal cells were obtained from explant primary culture, established in DU145 cell conditioned medium and maintained in RPMI-fetal bovine serum (FBS) supplemented with insulin, transferrin and selenium (ITS).

Androgen responsiveness of stromal cells of the human prostate: regulation of cell proliferation and keratinocyte growth factor by androgen.

Purpose: Growth and development of the prostate are androgen dependent and mainly influenced by stromal-epithelial interaction. It is believed that indirect androgenic activation of paracrine factors like keratinocyte growth factor (KGF) in the prostatic stroma influences the growth of epithelial cells. In this study we investigated the role androgen plays in stromal cell growth and stimulation of KGF in the human prostate.

Intestinal ammonium transport by ammonium and hydrogen exchange.

Background: Ionized ammonia (NH3) transport in the intestine has not been previously established as a mechanism of acidosis in urinary intestinal diversion or hepatic failure.

Study Design: The purpose of this study was to establish that ionized transport of ammonium (NH4) occurs in the intestine and to characterize the mechanism of its transport using the methodology of brush border membrane vesicles and acridine orange fluorescence.

Results: An NH4/H exchange was demonstrated and found to be the dominant mechanism causing a pH change when NH4 is transported across the lumenal membrane.

Photodynamic destruction of lysosomes mediated by Nile blue photosensitizers.

Previous studies have established that a number of Nile blue derivatives are potent photosensitizers and that they are localized primarily in the lysosomes. The present study examines whether the lysosome is a main target of the photocytotoxic action mediated by these sensitizers. Chosen for this study were NBS-6I and sat-NBS, which represented, respectively, derivatives with high and moderate degrees of lysosomal.

Lysosomal localization and mechanism of uptake of Nile blue photosensitizers in tumor cells.

Nile blue derivatives have been shown to be potentially effective photosensitizers for photodynamic therapy of malignant tumors. Results of a previous study suggested that the high accumulation of these dyes in cells may be the result of dye aggregation, partition in membrane lipids, and/or sequestration in subcellular organelles. In this report, results of studies are presented from an investigation of the subcellular localization and mechanism of accumulation of these dyes in cells in vitro.

Detection of exfoliated bladder cancer cells by monoclonal antibodies to tumor-associated cell surface antigens.

Monoclonal antibodies (Mabs) to human tumor antigens have potential for tumor detection and treatment. For bladder carcinoma, the detection of exfoliated tumor cells in urinary specimens may be accomplished with Mabs reacting to tumor cell-surface components. This method may be useful for screening and monitoring carcinogen-exposed workers.

Detection of tumor cells in bladder washings by a monoclonal antibody to human bladder tumor-associated antigen.

We have conducted two studies to evaluate the efficacy of using a specific monoclonal antibody (McAb) to detect exfoliated tumor cells in bladder washings. This is a preliminary step toward the development of immunological methods to improve the cytologic detection of bladder carcinoma. In this study, McAb 3G2-C6 was used.

Visualization of urothelial blood group isoantigens A and B using direct biotin-labeled antibodies and avidin-biotin-peroxidase complex.

The loss of blood group isoantigens from the surface of bladder tumor cells has been correlated with the potential invasiveness of the tumor. Development of simple and reliable methods for detection of these isoantigens should facilitate the general clinical use of this test for predicting malignant potential in low grade, low stage cancer of the bladder. We now report a direct peroxidase technique for the detection of isoantigens A and B by utilizing the specific interaction between biotin and avidin, and the capability of labeling a single antibody with multiple biotin molecules.

Tumor and placental histaminase, I. affinity chromatography purification and characterization of the placental enzyme.

Histaminase (diamine oxidase) is an enzyme produced at very high levels by the decidua of the placenta and is found to be associated with a number of human cancers. A procedure for the affinity chromatography purification of this enzyme is described. In this procedure, cadaverine-AH-sepharose was used to bind the enzyme in the placental extract.