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. Exposure to chronic low levels of estrogen results in development of endometrial cancer, similar to that observed in the postmenopausal female. In vitro and in vivo studies demonstrate that levels of Cables mRNA in benign human endometrial epithelium are up-regulated by progesterone and down-regulated by estrogen. Furthermore, nuclear immunostaining for Cables is lost in a high percentage of cases of human endometrial hyperplasia and adenocarcinoma, which are likely the product of unopposed estrogen. The loss of Cables immunostaining in the human endometrial cancer samples correlates with a marked decrease in Cables mRNA. Ectopic expression of Cables in human endometrial cells dramatically slows cell proliferation. Collectively, these data provide evidence that Cables is hormonally regulated and is involved in regulating endometrial cell proliferation. In addition, loss or suppression of Cables may be an early step in the development of endometrial cancer.

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. This is indicated by the light-and drug-dose-dependent losses of acid phosphatase staining particles, reduction of hexosaminidase in the lysosome-containing subcellular fraction, and impairment of the lysosomes to take up and sequester acridine orange. Ultrastructurally, swollen and ruptured lysosomes were seen as one of the first evidences of cell damage mediated by these photosensitizers. However, the study also showed that sat-NBS, which is less lysosomal selective, was less effective in mediating lysosomal destruction. Also, the degree of lysosomal destruction mediated by sat-NBS did not parallel the degree of cytotoxicity generated. This implies that for derivatives that are not exclusively localized in the lysosome, other subcellular sites may also be damaged by the photodynamic action and may play a role in the photocytotoxic process.

These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth.

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. Chromosome 18q loss of heterozygosity (LOH) was evaluated with multiple polymorphic markers. Cables inhibited cellular proliferation and colony formation in colon cancer cell lines. Colorectal cancer (CRC) is characterized by several unique features that make it well suited for the study of the molecular genetics of tumor progression. A stepwise model of colorectal tumorigenesis has been well defined and validated. 1 The inactivation of the adenomatous polyposis coli tumor suppressor gene is an early event that leads to the development of polyps, followed by oncogenic KRAS mutations in the adenomatous stage. Later events include deletions on chromosome 18q and inactivation of the tumor suppressor gene TP53 on chromosome 17p with the transition to malignancy.Chromosome 18q is lost in a high proportion (approximately 70%) of CRCs. 2 There are many candidate tumor suppressor genes on chromosome 18q, including deleted in colon cancer (DCC), SMAD4 (DPC4), and SMAD2. 3-5 DCC was recently shown to be the netrin-1 receptor. 6 DCC is expressed in normal colonic mucosa and in both primary and metastatic colonic cancer. 7 However, mice lacking the functional DCC gene do not develop colon tumors. 8 The SMAD proteins mediate transforming growth factor-␤ effects and regulate genes involved in cell cycle control. SMAD4 is biallelically inactivated in approximately 60% of pancreatic cancers. 9 However, the number of mutations identified in the SMAD genes has been relatively small in colorectal cancer.