Of Oncogenes And Target Cells...

Bipotency
UberAllesVille


I started gradual school 40 years ago.

Luckily for me, a very smart woman agreed to let me come and work in her lab to try and figure out if subtle differences in a target cell would affect the type of cancer you would produce after you introduce a powerful 'oncogene' into those cells.

We chose cells from the outer part adrenal gland as the targets because, as they develop down a 'lineage', they exhibit subtly different characteristics that based on the type of steroids they synthesize and secrete.

When I started this work I had know idea that I would actually spend the first few years first isolating, then separating, and, finally, characterizing those different steroid-secreting target cells.

Then, in the end, I had to figure out how to keep the different cell types alive in a culture dish so that I could whack them with a nasty little bug called the Kirsten Murine Sarcoma Virus.

Why?

Because the genome of that virus codes for a very strong oncogene called K-Ras.

And the product of the K-Ras oncogene is an oncoprotein that turns all kinds of target cells into tumor cells when you ram it into them experimentally.

And why does it do that?

Because the oncoprotein interacts with and 'turns on' a series of signaling proteins located inside the cell that drive the uncontrolled division of that cell.

And it turns out that the K-Ras oncogene is also present in a large number of real (i.e. not just experimental) tumours in actual people, including the most aggressive, hard-to-treat, and very often deadly, pancreatic cancers.

You may have read or heard about a recent 'breakthrough' treatment for aggressive pancreatic cancer that involves the use of a revolutionary new drug.

As you might imagine given the set-up here, that drug blocks the activity of the K-Ras oncoprotein.

We'll discuss how that works next time. It's really quite ingenious and, to foreshadow things a little, the drug acts by preventing the interaction of the oncoprotein with almost all of those signaling proteins that drive cell division in the ontogenically-transformed tumor cell.

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Image at the top of the post?...Individual rat adrenal cells that can either become steroid secreting or goopy matrix producing cells sticking to the bottom of the culture dish. Because they can produce two cell types we described these cells bipotent and stem-like...The little bright, black-rimmed spots that are packed into most of the cells are actually tiny droplets of lipid that hold the cholesterol that forms the chemical backbone of steroid hormones.