PubMed Health⌕ Search

Biomedical subjects

A K Rustgi

Publications and source records attributed to A K Rustgi.

At least 73 records · Page 4Linked to original sources
PubMed1995

MTS-1 (CDKN2) tumor suppressor gene deletions are a frequent event in esophagus squamous cancer and pancreatic adenocarcinoma cell lines.

MTS-1 is a candidate tumor suppressor gene on chromosome 9p21-22, a region frequently observed to have loss of heterozygosity in esophagus squamous cell carcinomas and pancreatic ductal adenocarcinomas. In order to determine whether MTS-1 sequences are deleted or mutated in cell lines derived from these cancers, we performed PCR amplification of MTS-1 exons 1 and 2. In this fashion, we found that 67% of esophagus squamous cancer cell lines have deletions of both exons 1 and 2, and 50% of pancreatic cancer cell lines have similar deletions. Furthermore, an additional 30% of pancreatic cancer cell lines harbored point mutations or microdeletions based on DNA sequencing. MTS-1 encodes p16, an inhibitor of cyclin-dependent kinase 4 (cdk4) which complexes with cyclin D1. Our data suggest that MTS-1 deletions and mutations may play an important role in the molecular pathogenesis of esophagus squamous cell and pancreatic cancers.

Adenocarcinoma↗
PubMed1995

Human papillomavirus-16 and -18 replication in esophagus squamous cancer cell lines does not require heterologous E1 and E2 proteins.

Human papillomaviruses (HPVs) are double-stranded DNA viruses that replicate in the nuclei of squamous epithelial cells. HPVs can be classified into high-risk (e.g., types 16, 18, 31, and 33) or low-risk (e.g., types 6, 11, and 30), depending on their association with benign or malignant tumors. We recently described the association of HPV-16 and -18 with esophagus squamous cell cancer. HPV replication was studied in representative cell lines derived from esophagus cancers. HPV-16 and -18 genomes were independently transiently transfected into HCE-4 and HCE-7 cell lines with and without E1 and E2 genes under heterologous promoters. Southern blot analysis demonstrated that these cell lines support viral replication. However, heterologous E1 and E2 are not required for HPV replication. These findings suggest that specific host nuclear factors in esophageal squamous epithelial cells may support HPV replication.

Blotting, Southern↗
PubMed1995

DNA mismatch repair and cancer.

The genetic basis of cancer involves certain classes of genes, particularly oncogenes, tumor-suppressor genes, and DNA mismatch repair genes. Originally identified in bacteria and yeast, the human homologues of DNA mismatch repair genes have been implicated in the pathogenesis of the hereditary nonpolyposis colorectal cancer syndromes, as well as a variety of different sporadic cancers. An appreciation of their role in cancer is predicated on an understanding of their function in the processes of DNA repair. This article reviews the recent developments and advances in the biology of the human DNA mismatch repair genes and their involvement in the pathogenesis of cancer.

Colonic Neoplasms↗
PubMed1995

A novel human papillomavirus sequence based on L1 general primers.

Over 65 human papillomaviruses (HPVs) have been identified. The majority have been isolated on the basis of cloning systems in bacteria. Recently, general consensus or degenerate primers from the L1 region have been used in PCR to identify novel genotypes. In this fashion, we employed general primers in the L1 region followed by DNA sequencing to identify a novel HPV sequence in association with esophageal squamous cell carcinoma.

Amino Acid Sequence↗
PubMed1994

Growth and intestinal differentiation are independently regulated in HT29 colon cancer cells.

The polar-planar compound hexamethylene bisacetamide (HMBA) can inhibit HT29 colon carcinoma cell growth and induce a more benign phenotype, as defined by decreased anchorage-independent clonogenicity, loss of a cell surface malignancy marker, and decreased in vivo tumorigenicity. The principle aim of this study was to determine whether HMBA's effects on HT29 cell growth and biologic behavior correlate with effects on intestinal differentiation. Parallel studies were performed with sodium butyrate (NaBT), a potent inducer of intestinal differentiation. HT29 cell growth, proliferation, and markers of intestinal differentiation were assayed after short- and long-term treatment with HMBA, NaBT, or the combination. Both 5 mM HMBA and 5 mM NaBT were potent inhibitors of monolayer growth; in combination their effects were nearly additive. Inhibition of DNA synthesis was detectable within 6 h of treatment and was preceded by down-regulation of c-myc expression. Soft agar clonogenicity was also decreased by 90%, > 99%, and > 99% by HMBA, NaBT, and the combination, respectively. Despite these parallel effects on growth and in vitro markers of a benign phenotype, effects on intestinal differentiation were discordant. NaBT induced significant increases in membrane-associated alkaline phosphatase activity, cytosolic mucin content, PAS+/diastase-resistant cells, and ultrastructural evidence of intestinal cell differentiation. HMBA not only failed to induce markers of intestinal differentiation, but attenuated NaBT's effects when used in combination. These data suggest that growth and intestinal differentiation may be independently regulated in HT29 cells. They also suggest that expression of intestinal markers of differentiation is not a prerequisite for the acquisition of a more benign phenotype.

Acetamides↗
PubMed1994

Human papillomavirus DNA sequences in esophagus squamous cell carcinoma.

BACKGROUND/AIMS: Esophagus squamous cell carcinoma has much geographic variation. A variety of genetic and environmental factors have been implicated in the pathogenesis of esophagus squamous cell carcinoma. This study was undertaken to determine whether the human papillomavirus is present in these tumors. METHODS: A radioactive nested polymerase chain reaction was used to determine the presence of human papillomavirus in esophagus squamous cell carcinoma DNA and adjacent normal mucosa DNA from different regions of the world. Restriction fragment length polymorphism analysis was used to determine which particular human papillomavirus genotype was present. RESULTS: Human papillomavirus was identified in 14% of esophageal squamous cell cancer DNA but in none of the adjacent normal mucosa DNA available for some of the samples. Positive samples were found to contain sequences specific for high-risk human papillomaviruses, either types 16 or 18. In addition, a novel human papillomavirus genotype was detected in another 10% of the samples. CONCLUSIONS: Esophagus squamous cell carcinoma is associated with the expression of human papillomavirus genotypes 16 and 18, which are linked to transformation of squamous epithelial cells. In addition, a novel human papillomavirus genotype that was identified may be associated with pathogenesis in esophagus squamous cell cancer.

Adult↗
PubMed1994

Radiolabeled polymerase chain reaction assay for detection of ras oncogene point mutations in tumors.

The human ras gene plays a fundamental role in the transduction of extracellular signals to the nucleus, thereby regulating cell growth and differentiation. Point mutations in the ras gene convert it into a transforming oncogene that has been found in many solid and hematologic malignancies. We describe a rapid and sensitive assay based on a radiolabeled polymerase chain reaction followed by restriction enzyme digestion that we have adapted for differentiating between the wild-type and mutant ras genes. This assay should prove useful in the analysis of ras gene point mutations in clinical tumor specimens in which ras oncogene activation is an early event in carcinogenesis.

Base Sequence↗
PubMed1993

TATA-binding protein and the retinoblastoma gene product bind to overlapping epitopes on c-Myc and adenovirus E1A protein.

Using a protein binding assay, we show that the amino-terminal 204 amino acids of the c-Myc protein interact directly with a key component of the basal transcription factor TFIID, the TATA box-binding protein (TBP). Essentially the same region of the c-Myc protein also binds the product of the retinoblastoma gene, the RB protein. c-Myc protein coimmunoprecipitates with TBP in lysates of mammalian cells, demonstrating that the proteins are also complexed in vivo. A short peptide that spans the RB binding site of the E7 protein of human papilloma virus type 16 interferes with the binding of c-Myc to TBP. The same peptide also blocks binding of adenovirus E1A protein to TBP, suggesting that c-Myc and E1A bind to RB and TBP through overlapping epitopes. Furthermore, we show that binding of RB to E1A prevents association of E1A with TBP. Our data suggest that one of the functions of RB and RB-like proteins is to prevent interaction of viral and cellular oncoproteins, such as c-Myc and E1A, with TBP.

Adenosine Triphosphate↗
PubMed1992

The molecular basis of colon cancer.

There are approximately 160,000 new cases of colon cancer every year in the United States. Colon carcinoma results from the aggregate effects of multiple genetic alterations. Some genetic alterations may be inherited, while others reflect somatic mutations. The latter may themselves be the indirect result of environmental factors such as diet. It is the total accumulation of these genetic changes, combining the activation of oncogenes with the inactivation of tumor suppressor genes, that is responsible for determining the biologic properties of colon cancer.

Cell Transformation, Neoplastic↗
PubMed1991

Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product.

The proteins encoded by the myc gene family are involved in the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/helix-loop-helix and a leucine zipper motif, respectively. These motifs are involved both in DNA binding and in protein dimerization. In addition, myc protein family members share several regions of highly conserved amino acids in their amino termini that are essential for transformation. We report here that an N-terminal domain present in both the c-myc and N-myc proteins mediates binding to the retinoblastoma gene product, pRb. We show that the human papilloma virus E7 protein competes with c-myc for binding to pRb, indicating that these proteins share overlapping binding sites on pRb. Furthermore, a mutant Rb protein from a human tumour cell line that carried a 35-amino-acid deletion in its C terminus failed to bind to c-myc. Our results suggest that c-myc and pRb cooperate through direct binding to control cell proliferation.

Amino Acid Sequence↗