Science Break! Outreach – Getting High School Students Excited About Cancer Research!

Last week, I had the opportunity to speak with students in Freshman Biology classes at Overton High School here in Nashville. I’d given science demonstrations before—including fun with dry ice and a mouse organ scavenger hunt/anatomy lesson that was fun for everyone except one squeamish student. But I’d never spoken in detail about cancer biology and cancer research.

I’ve been saying (read: complaining) for YEARS about how scientists are terrible about speaking with the public. We talk to each other all the time at our institutions and at scientific conferences, but not enough of us reach out to our communities, and that’s a shame. First of all, we as scientists should be advocates for the scientific process and for the progress we’re making. Second, scientists are in a position to combat scammers, pseudoscience, and mis/disinformation by sharing our knowledge. Third, most of us are funded, at least in part, by the federal government. I’m funded by The National Institutes of Health (NIH) through The National Cancer Institute (NCI) – those agencies are funded by federal tax dollars. Since I’m paid by tax dollars, I personally feel an obligation to be able to explain what I do and why it is important to taxpayers in terms they can understand.

So, in my new role as a cancer researcher who has also survived cancer, I’m putting my time and effort where my big fat mouth is and getting out there to be an ambassador and advocate for cancer research! I occurred to me that the slides from my recent presentation for high school students would make a great addition to this blog. It covers how normal cells transform into malignant tumor cells at the molecular level.

The goal of this presentation is to provide a brief overview of how damage to DNA, the genetic code that is used to build proteins (the workhorses of a cell) can lead to uncontrolled cell growth and survival – both hallmarks of cancer. Damage to DNA and failure to properly repair that damage can lead to mutation (change in the code), amplification (more copies of a gene than normal), deletion (loss of DNA and the genes encoded). When changes in DNA occur in genes that regulate cell division, this can contribute to cancer. Uncontrolled cell growth is fundamental to cancer.

To understand how DNA damage leads to cancer, we first have to review what DNA actually does – The Central Dogma of Molecular Biology. I covered this in a previous post, but I’ll go over it again for the (vast majority of) people who don’t spend their days thinking about and doing molecular and cellular biology research. The more frequently you see information, the more likely you’ll be to remember it.

DNA is the blueprint that contains instructions for how to build every protein a cell needs for its normal function. Since, as we’ll see in the next few slides, DNA damage can cause huge problems for cells, DNA is protected in an organelle within the cell called the nucleus. It is only unwound from its double helix structure during (1) DNA replication when the cell makes extra copies before dividing, and (2) when tiny portions, genes, are transcribed (copied) into small units called RNA. RNA gets transported out of the nucleus where the code is translated to make proteins. Each sequence of three base pairs encodes a specific amino acid (building blocks of protein). Take home = DNA to RNA to protein. And DNA damage leads to problems with the proteins they encode.

So what do proteins do? The answer is pretty much everything a cell needs to function. Two specific classes of proteins, those involved in regulation and signaling, are the targets of mutations/amplifications/deletions that can lead to cancer. Regulation involves turning cellular processes, like cell division, on and off. Signaling involves proteins transmitting messages from outside the cell to the inside — including messages that tell the cell when to divide.

DNA can be damaged or altered by internal factors and external factors. Errors occur in replication (copying during cell division), and if they aren’t repaired properly, they can lead to mutations. Other things that can damage DNA include ultraviolet light (sunlight – skin cancer), chemicals (carcinogens) in cigarette smoke, and exposure to radiation. Base mismatches can lead to a change in the code. Single-stranded and double-stranded breaks can lead to amplification or deletion of essential genes in the cell division process. Damage to DNA in genes that encode DNA damage repair proteins are especially harmful, as failed repair leads to more mutations, amplifications, and deletions that accumulate and lead to cancer.

Mutations and DNA damage occur relatively infrequently. Most mutations are silent, meaning that they don’t affect the production or function of the protein the gene encodes, and it takes more than one mutation to transform a cell and make it cancerous.

The types of genes that drive cancer include oncogenes and tumor suppressors. In the cell division process, there are many on/off switches that tell the cell when to divide and when to stop the process of division. Oncogenes, which are amplified (more copies of the gene than normal made after DNA damage) or mutated to be super active, are the “go” signals, like a car’s accelerator. Tumor suppressors, which are deleted (genes are lost after DNA damage) or mutated to be non functional, are the “stop” signals, like a car’s brakes. A combination of amplified/mutated oncogenes plus deleted/mutated tumor suppressors transform a normal cell into a cancer cell that then divides uncontrollably, like a speeding car with the brake lines cut.

On/off switches in the cell cycle, the series of steps that a cell follows to divide and make two cells, have the potential to become oncogenes and tumor suppressors.

This slide shows an example of an oncogene and tumor suppressor in a signaling pathway that contributes to breast cancer. Cyclin-dependent kinases (CDK) are enzymes that tag other proteins with phosphates (P) groups, which serves as a signal for the tagged protein to perform its function. In the case of CDK4/6, its substrate RB (off switch for cell cycles) is tagged with phosphate, which marks it for destruction by the cell. When RB is destroyed, it releases its buddy E2F, freeing it to help the cell make more proteins required for cell division. CDK2/4 function is activated (on switch for cell cycle) by binding to its buddy cyclin D1, and is deactivated by its inhibitor p16. The gene encoding cyclin D1 is commonly amplified (more copies) in breast cancer, and the gene encoding RB is commonly mutated or deleted (gene lost or mutated to make a non functioning protein). Thus, cyclin D1 is an oncogene, and RB is a tumor suppressor.

That’s the overview, but this time I include specific examples. There are many other oncogene drivers and tumor suppressors that contribute to breast cancer and other cancers. I’ll cover some of those in future posts. Hope y’all enjoyed this Science Break! Shout out to Dr. Shannon Youngman and the students from Overton for hosting me and asking some great questions!

Science Break! Cancer 101: How Normal Cells Become Transformed Into Cancer

Cancer has been with us since we became human, and probably before, since cancer isn’t common to our species. In a fundamental way, cancer is us. Cancer was once healthy tissue, starting out as a cell in your body fulfilling its function to keep the collective whole, you, functioning. This cell toed the line, divided when it was supposed to, stopped dividing when it was supposed to, differentiated and specialized to perform its function, and if it had remained normal, it might have died when told to do so after that function was fulfilled. Those are three of the hallmarks of cancer: uncontrolled cell division (cells making more cells), failure to respond to the normal programs that put the brakes on cell division, and failure to undergo programmed cell death (die when the time is right).

The process by which a normal cell becomes cancerous is called malignant transformation or carcinogenesis. This video provides an excellent overview of the process.

To understand how cancer forms, we need a basic framework for understanding cellular function and its regulation at the molecular level. Don’t get bogged down in the terms. Cellular function refers to how the cell does its programmed job, how it grows and divides, and how it dies, the same basic life cycle that the human host experiences. Regulation at the molecular level means the plan the cell follows, the blueprint for its growth, function, and death. It starts with DNA, the double helix genetic blueprint in all cells that contains the instructions for the cell’s functions and life plan.

Illustration of the Central Dogma of Molecular Biology – Nuclear DNA is transcribed to an intermediate, called RNA, which is then used as a template for translation into amino acid chains that form proteins. Illustration credit: Shutterstock.

So what does DNA actually do, or perhaps the better question, how does the information encoded in DNA actually instruct the cell what to do? This gets into something call the Central Dogma of Molecular Biology. That’s a fancy title for the way in which the instructions encoded in DNA are used to manufacture proteins, the work horses of cells. Now, when most people think about proteins, they envision a juicy piece of meat or powerful muscles, and the components used to build muscle fibers are proteins. But proteins are much more than that. They are the essential building blocks of cells, which in turn build tissues, organs, and all parts of the body. They can be structural, like the fibers that form the cell’s cytoskeleton and histone proteins that wrap around DNA strands and protect them. They can be functional, forming enzymes that do everything from metabolize nutrients, breaking them down into usable building blocks for building biomass and generating energy for the cell. They also play a critical role in transmitting information within cells and between cells, integrating communication between different parts of the body.

Proteins are made up of chains of amino acids, and the order in which they are put together is determined by the sequence of the portion of DNA that encodes that protein. That sequence is called a gene. But as a matter of practicality, since DNA is housed in a subcellular organelle called the nucleus and therefore inaccessible to the protein production machinery in the cytoplasm, and because the cell needs to protect the integrity of its DNA, proteins are not built using pieces of actual DNA. The portion of the DNA, the gene, that encodes instructions for making a specific protein, is first transcribed into an intermediate molecule, call messenger RNA. Transcriptional machinery within the nucleus unwinds and separates the DNA strands, using one strand to copy the information necessary to build a protein. The messenger RNA molecule is then transported out of the nucleus and used by the protein synthesis machinery to translate the information encoded by the mRNA to protein. That’s the Central Dogma: DNA transcribed to RNA, and RNA translated to protein.

The abnormal growth that is cancer is controlled by abnormal proteins that were once (supposed to be) normal proteins. Most of the proteins that drive cancer are proteins that regulate cellular division and cellular survival, and they fall into two basic categories: oncoproteins and tumor suppressors. Oncoproteins are hyperactive proteins that start out as normal proteins, encoded by normal genes, proto-oncogenes. They become oncogenes due to alterations in DNA: mutations that change the DNA sequence, which in turn changes the amino acid encoded and the function of the protein; DNA repair mistakes that cause multiple copies of genes (amplification) to produce too much of a protein that drives growth and survival; changes in DNA that make the gene more accessible, which in turn causes the cell to make more copies of the encoded protein. DNA damage that causes breaks, which can eliminate genes that normally keep cell growth controlled, can silence tumor suppressors.

Types of DNA damage – if damage is not repaired or is improperly repaired, alterations in DNA (e.g. mutations, deletions, amplifications) that encodes growth and/or survival genes can lead to malignant transformation of a normal cell into a cancer cell. Link to photo source.

What’s worse is that the longer the cancer grows unchecked, the more mutations and DNA changes it collects. Those alterations and mutations that give the cell an advantage (more growth, better survival, the ability to break away from the tumor mass and spread) make the cancer more aggressive and difficult to treat.

Cancer Formation and Abnormal Growth – Illustration credit: Deposit Photos.

In my next post, I’ll cover the process of malignant transformation of breast cells, which leads to breast cancer.

Screw the Woo Woo: For The Love of The Flying Spaghetti Monster Do NOT Sun Your Bunghole!

Beavis and Butt-head are the intellectual property of
Mike Judge.

In this installment of Screw The Woo Woo, I’m tackling a “wellness” trend that’s been making the rounds on social media, including my Facebook feed, and that is disturbing on sooooooooo many levels: butthole sunning. At first, I thought it was a joke. I really, REALLY hoped it was a joke. Then again, jade eggs for the vagina, vagina steaming, and coffee enemas were (and apparently still are) a thing, so what’s one more bizarre bit of ridiculousness in the wooniverse? This isn’t directly related to breast cancer, BUT(T), since ultraviolet light from the sun can cause skin cancer, I’ve decided to tackle the subject and debunk its alleged benefits to, er, bring to light the very real dangers of exposing your junk to the sun.

That and one of the proponents of this weird ass practice is making shady claims about how butthole sunning balances hormones in the sex organs. It doesn’t. More on that later.

First off, the notion that sunlight can enter your body through your vagina or anus is ludicrous, as is the notion that butthole sunning prevents the leakage of “chi” from the body, mostly because “chi” isn’t a thing, and if you’re experiencing any kind of leakage from your anus or genitals, you DEFINITELY need to seek your doctor. The vagina doesn’t just magically open to the heavens like a flower when you open your legs to the sun. Don’t believe me? Read The Vagina Bible by Dr. Jen Gunter, M.D. and gynecologist who covers everything you need to know about care and maintenance of your girly parts.

In addition to blocking chi leakage, woo woo practitioner MetaphysicalMegan (~a clearly qualified source of accurate, reliable information~) claims that sunning your perineum (a.k.a. the taint, the gooch, the fleshy fun bridge) provides a myriad of health benefits (link to a story that shares her tweet – I refuse to link directly to woo woo bullshit sites) – such as regulating “hormone function in the sex organs.”

That claim is a GIANT steaming pile of bullshit.

Hormone function in sex organs is regulated by intracellular hormone receptors expressed in the cells of internal sex organs that are well-protected from the outside world, including sunlight. For example, estrogen receptors in females are expressed in mammary glandular epithelium deep within breast tissue (where they can contribute to the growth of breast cancer cells in ER+ disease), the endometrial tissue that lines the uterus (internal organ protected from sunlight), ovary, bone (which is why bone loss is a concern for menopausal women and breast cancer patients on estrogen suppression therapy – estrogen contributes to cellular signaling pathways that promote bone growth), and other organs and tissues that are protected from the elements. As sunlight cannot reach estrogen receptor expressing cells, it cannot influence the function of estrogen signaling within them.

But what’s the harm, you might ask? Lots of people believe in and incorporate New Age and Wellness practices into their daily lives. Well, in this case, exposing delicate skin to ultraviolet sun rays without the benefit of sunscreen can actually be harmful. Ultraviolet light breaks bonds in the nucleotide bases (thymine and cyotsine) of DNA in skin cells that absorb it. This can facilitate abnormal bonding between adjacent thymine (thymine dimers) and cytosine (cytosine dimers) that form kinks in DNA. If not repaired, this can lead to DNA mutations that contribute to the development of skin cancers. Now, MetaphysicalMegan recommends 30 seconds, but given that every second you are in the sun, 50 to 100 of these dimers are formed in each skin cell. That’s a hell of a place to risk getting skin cancer, not to mention that the proverbial “places where the sun don’t shine” are horrible places to get a freakin’ sunburn!

Bottom (giggle snort) line: exposing your asshole/taint/vagina/penis/nutsack to the sun isn’t going to help your health. It’ll probably give you a sunburn, it can increase your risk of skin cancer, and it will most certainly make you look like a fucking idiot. Don’t do it.

Publicly available references from The US National Library of Medicine, National Institutes of Health: Estrogen receptor expression and function in female reproductive disease; Estrogen receptors and human disease: an update

*Apparently Josh Brolin tried butthole/perineum sunning and, not surprisingly, regretted it. Yup, not even Thanos can handle that flavor of sick burn. The evil part of me REALLY hopes that Ryan Reynolds works in some butthole sunning jokes at Cable’s expense in the next Deadpool film!

Maybe they’ll even do a little superhero bro bonding with joint butthole sunning. They could even bring along Colosus and Dopinder.

I mean, who DOESN’T want to see dat ass? You’re picturing it. I know you are!