Ha-ras-1 oncogene mutations in mammary epithelial cells do not contribute to initiation of spontaneous mammary tumorigenesis in rats

Carcinogenesis
R S ChaHelmut Zarbl

Abstract

We have previously shown that oncogenic GGA to GAA mutations in codon 12 of the Ha-ras-1 gene arise spontaneously during normal development of the mammary epithelium of female Fischer 344 (F344) rats. Our result further demonstrated that the vast majority of nitrosomethylurea (NMU)-induced rat mammary tumors with Ha-ras-1 oncogenes arose from these pre-existing mutants. We therefore investigated whether Ha-ras-1 mutants acquired a selective growth advantage in vivo in the absence of NMU exposure. Our results indicated that between the ages of 50 and 570 days, the total number mammary epithelial cells per rat increased approximately 5 fold (from 3.7x10(7) to 1.8x10(8) cells), while the average number of Ha-ras-1 mutants per rat increased approximately 25 fold (from 160 to 4000 cells). Thus, the mutants acquired a measurable (5-fold) growth advantage in vivo. To determine if the growth of these mutants contributed to spontaneous mammary carcinogenesis, we measured Ha-ras-1 mutant fractions in 26 tumors from untreated F344 rats. The assay failed to detect Ha-ras-1 mutant fractions higher than 10(-3), indicating that in the mammary epithelium, the activating mutation of the Ha-ras-1 gene is a conditional oncomutation, whose oncogen...Continue Reading

Citations

Aug 6, 2004·Journal of Biosciences·Rita Mulherkar
Dec 31, 1997·Mutation Research·B L Parsons, R H Heflich
Aug 13, 1998·Journal of the National Cancer Institute·K S IwamotoT Seyama
Jan 6, 2009·Cancer Prevention Research·Xun Zhang, Helmut Zarbl
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·M Chow, H Rubin
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·M Chow, H Rubin
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·M Chow, H Rubin
Feb 3, 2005·International Journal of Cancer. Journal International Du Cancer·Tatsuhiko ImaokaYoshiya Shimada
Apr 15, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Harry Rubin
Nov 30, 2006·International Journal of Cancer. Journal International Du Cancer·Thea M GoepfertW R Brinkley
Jul 24, 2008·Molecular Carcinogenesis·Emma SamuelsonAfrouz Behboudi
Oct 10, 2013·International Journal of Cancer. Journal International Du Cancer·Tatsuhiko ImaokaYoshiya Shimada
Sep 20, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Paula C MailanderDhrubajyoti Chakravarti
Feb 7, 2006·Mutation Research·Hiroko SudoWilliam G Thilly
Aug 11, 2020·Cancer Metastasis Reviews·Erzsébet Rásó
Oct 28, 2005·The American Journal of Pathology·Maricel V MaffiniCarlos Sonnenschein
Mar 5, 2004·Journal of Cell Science·Maricel V MaffiniCarlos Sonnenschein

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.