Temporal/spatial expression of retinoid binding proteins and RAR isoforms in the postnatal lung

Endogenous retinoids have been implicated in alveologenesis in both the rat and the mouse, and exogenous retinoic acid (RA) can reverse or partially reverse experimental emphysema in adult rat and mouse models by an unknown mechanism. In this study, we examine the cellular and molecular biology of retinoid signaling during alveologenesis in the mouse. We describe the temporal and spatial expression of the retinoid binding proteins CRBP-I, CRBP-II, and CRABP-I using RT-PCR and immunohistochemistry. We identify the retinoic acid receptor isoforms RAR-alpha 1, RAR-beta 2, RAR-beta 4, and RAR-gamma 2 and describe their temporal and spatial expression using RT-PCR and in situ hybridization. We demonstrate that both retinoid binding proteins and RAR isoforms are temporally regulated and found within the alveolar septal regions during alveologenesis. These data support a role of dynamic endogenous RA signaling during alveolar formation.     

Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor

The ING1 gene encodes p33(ING1), a putative tumor suppressor for neuroblastomas and breast cancers, which has been shown to cooperate with p53 in controlling cell proliferation. We have isolated a novel human gene, ING1L, that potentially encodes a PHD-type zinc-finger protein highly homologous to p33(ING1). Fluorescence in situ hybridization and radiation-hybrid analyses assigned ING1L to human chromosome 4. Both ING1 and ING1L are expressed in a variety of human tissues, but we found ING1L expression to be significantly more pronounced in tumors from several colon-cancer patients than in normal colon tissues excised at the same surgical sites. Although the significance of this observation with respect to carcinogenesis remains to be established, the data suggest that ING1L might be involved in colon cancers through interference with signal(s) transmitted through p53 and p33(ING1).     

Peroxisome proliferator-activated receptors modulate proliferation and angiogenesis in human endometrial carcinoma

Peroxisome proliferator-activated receptors (PPAR) and retinoid X receptors (RXR) are implicated in the development of several obesity-related cancers. Little is known of either the expression or function of PPARs and RXRs in endometrial cancer although this increasingly common disease is highly associated with both obesity and insulin resistance. We investigated the expression of PPAR and RXR subtypes in human endometrial cancers and normal endometrium with immunoblotting and immunohistochemistry and subsequently showed PPAR/RXR binding preferences by coimmunoprecipitation. To determine the functions of PPARs within the endometrium, we investigated proliferation, apoptosis, PTEN expression, and secretion of vascular endothelial growth factor (VEGF) in endometrial cell lines after reducing the expression of PPARα and PPARγ with antisense RNA. The functional effects of PPAR ligands were also investigated in vitro. We identified differential expression of PPAR and RXR subtypes in endometrial cancers and discovered that PPARγ expression correlated with expression of PTEN. PPARα activation influences endometrial cell growth and VEGF secretion. PPARγ activation reduces proliferation of endometrial cells via regulation of PTEN and appears to reduce VEGF secretion. We conclude that the PPAR/RXR pathway contribute to endometrial carcinogenesis by control of PTEN expression and modulation of VEGF secretion. We propose that PPAR ligands should be considered for clinical investigation in early phase studies of women with endometrial cancer.     

Herpesvirus RNA in human urogenital tumors

In situ hybridization was used to examine human urogenital cancers for herpes simplex virus type 2 (HSV-2) and human cytomegalovirus RNAs. Neither of these herpes RNAs was found in prostate tissues. However, HSV-2 RNA was detected in premalignant and malignant cervical tissues.     

Expression profiles of SV40‐immortalization‐associated genes upregulated in various human cancers

Immortalization is an early and essential step of human carcinogenesis which is associated with alterations in gene expression and regulation. Suppression subtractive hybridization (SSH) was successfully performed to identify immortalization‐associated genes upregulated in SV40‐immortalized lung fibroblasts. We identified 116 known genes which were related to diverse functions, with 32.8% relevant for cell cycle or proliferation indicating the potential involvement of these genes in immortalization. We chose eight known genes located on the overrepresented chromosomes of non‐small‐cell lung cancers (NSCLCs). ASPM, RFC4, C3orf26, BXDC2, C15orf44, AURKA, C20orf77, and RBMX were upregulated in immortalized cells, cancer cells, and non‐small‐cell lung cancer (NSCLC) tissues. We additionally cloned two novel genes (CHA‐V‐97 and CHA‐V‐165) which showed similar upregulated expression patterns in cells and tissues examined. Identification and further characterization of these genes may provide insights of novel players for immortalization and human carcinogenesis. J. Cell. Biochem. 106: 703–713, 2009. © 2009 Wiley‐Liss, Inc.