Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.
Methylation is a natural genomic process that cuts two ways. It protects newly formed cells by getting rid of harmful genes, but also shields cells from tumor suppressor genes thus promoting cancer.
“Methylation,” explained tumor oncologist Stephen Baylin, “is the one change that we make to DNA after we replicate it, put in the four bases adenine, guanine, cytosine and thymine and have the right sequence. There’s one modification that we make to our DNA,” he added, “which is to put a methyl group CH3 on cytosines. Most of our genome is heavily methylated, perhaps because it helps to suppress unwanted expression of viral sequences that we all have integrated into our genome repeat sequences.
“But around the start site of key genes that you want to have expressed,” Baylin continued, “those regions are protected from methylation. In some way it may form a barrier so certain enzymes can’t get to those areas and methylate them. In cancer cells there’s a shift in the methylation pattern such that many important genes that ought to be active like tumor suppressor genes actually get hypermethylation around these start sites, thereby suppressing the tumor suppressors. Another way of losing the tumor suppressor gene’s function,” he went on, “is epigenetic silencing. That’s where you have a mutation in the readout region of that gene, so its protein is abnormal, or not even made.” (See BioWorld Today, March 30, 2002, p.1.)
Baylin, at Johns Hopkins University in Baltimore, is co-senior author of a paper in Nature dated April 4, 2002. Its title: “DNMT1 and DNMT3b cooperate to silence genes in human cancer cells.” It reports a previously unpredicted effect: that those two enzymes, responsible for DNA methylation, work together to silence genes that otherwise would stop human cancer cells from proliferating. The article’s findings establish that methylation is essential for gagging tumor suppressor genes at least in colorectal cancer cells.
Herceptin Sets Up Antitumor Constabulary Of Angiogenesis-Crimping Drug Combo
Cocktails are gradually replacing straight-ups in therapeutic, on-the-house drug-regimen barrooms. One such is Genentech Inc.’s Herceptin, which targets metastatic breast tumors. It’s a recombinant humanized antibody that binds to the human epidermal growth factor receptor (hEGFR). There it blocks proliferation of tumor cells that overexpress the Her-2/neu gene. But it doesn’t act as a loner.
Tumors secrete angiogenesis factors that supply the malignancy with a network of blood vessels loaded with oxygen and nutrients. Numerous anti-angiogenic drugs are in clinical trials, but the growing tumors soon beat them back with drug resistance factors. Hence a brief communication in Nature dated March 21, 2002, bears the title: “Herceptin acts as an anti-angiogenic cocktail.”
Rabbits Join Lengthening List Of Four-Footed Cloned Mammals That Began With Dolly
You’d think rabbits needed no outside help reproducing, but French molecular agronomists have successfully cloned the long-eared, randy bunnies from adult stem cells. Rabbit models of human disease notably atherosclerosis and cystic fibrosis are attractive, they point out, as their physiology matches primates, including Homo sapiens, more closely phylogenetically than do laboratory rats or mice.
Nature Biotechnology for April 2002 reports their feat in an article titled: “Cloned rabbits produced by nuclear transfer from adult somatic cells.” They are authors are developmental biologists at the National Institute of Agronomic Research in Jouy-en-Josas, France, in the exurbs of Paris.
Rabbits, their paper points out, “are one of the mammalian species considered up to now as difficult to clone.” The team started out by following procedures used in cloning other animals, beginning with Dolly the sheep. They first removed the nucleus from a female rabbit’s egg at a precisely timed stage, then electricofused it with an adult cell from a donor rabbit, which provided the nuclear material to be cloned.
The authors attribute their success where others have failed to clone rabbits in that they minimized the time that the fused cells were in the presence of various chemical agents that while necessary for the cells to start developing adversely affect later stages of embryo development. They also fine-tuned the exact narrow time window for implanting 91 embryos into surrogate rabbit mothers. On day 31 after embryo transplantation, the team delivered six neonatal kits by Caesarian section. Two, of normal appearance and weight, died one day after birth. The remaining four progeny showed normal growth and fertility. Two of the four, when tested for fecundity by natural mating, gave birth to seven and eight healthy kits, respectively.
Controversial Cloned Kitty Raises Questions For Genetic Replacement Market Of Feline Pets
Meanwhile, a pussycat has joined those four bunny rabbits in the cloned-mammal parade. The same April issue of Nature Biotechnology runs a photo of a small white-and-tabby kitten preening her image in the mirror. Its brief account carries the headline: “Operation copy-cat creates first feline clone.”
The item summarizes a fuller article in Nature dated Feb. 2, 2002. It leads off by describing Cc as “the first domestic pet successfully cloned by nuclear transfer,” and added, “The research was funded by Genetics Savings & Clone (GSC, College Station, Texas), a company created in February 2000 to clone pets, livestock, endangered species and rescue dogs.” While criticized for planning to add more cats to the millions of pets abandoned or destroyed each year because of adopter shortage, GSC protests “the $250,000 or so that it paid spay clinics in 2001 for eggs can in turn be used to spay more animals, keeping unwanted pet populations low.”
While families and individuals bereaved of their departed kitties seemingly constitute a large and loving market for Xeroxed erstwhile pets, clones rarely resemble their genetic progenitors in morphology or purrsonality, given the epigenetic and environmental influences that mold their attributes after birth.