Activating BRCA1 and BRCA2 with Estrogen

Nina VaniEnglish 302-N14

Introduction

• Breast cancer is the most common type of cancer in women and the leading cause of mortality in women.

• Inherited or cause by extra cellular growth. • Diagnosed as a result of an abnormality seen

on a mammogram.• Warning signs: a lump or change in

consistency of the breast tissue.• Recent Research shows that genetic and/or

hormonal factors are the primary risk factors for it.

Hereditary

• Cancer is a hereditary disease. – People can inherit the gene that causes

cancer.

• Inherit mutated genes– BRCA 1– BRCA 2– BRCA1 and BRCA2 are human genes that

belong to a class of genes known as tumor suppressors.

• Mutation of these genes has been linked to hereditary breast and ovarian cancer.

Mutations

• A gene mutation is a permanent change in the DNA sequence that makes up a gene.

• Occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime.

• Women who have inherited gene mutations BRCA1 or BRCA2 have up to an 85% risk of getting breast cancer, compared with 13% of women in the general population.

• Affects men equally.• Even when one inherits the mutated gene, the

gene can remain inactive and the person may never develop breast cancer.

Hypothesis

• The purpose of this research paper is to test which biological activity like increase in hormone estrogen lead to activation of BRCA1 and BRCA2 genes. – When and how are the BRCA1 and BRCA2

mutated genes triggered in starting abnormal activity that leads to breast cancer?

Estrogen

• Used therapeutically and to relieve symptoms of menopause in women for decades.

• The dosage of estrogen present in ones body has shown to increase concerns about the risk of both breast and endometrial cancers.

Experimental Design

• The purpose of this research experiment is to observed and determine at what point in cell cycle an increase in estrogen causes activation of BRCA1 and BRCA2 leading to breast cancer.

• Tested on mice.

Procedure

• The mice will be created through in-vitro thus BRCA1 and BRCA2 mutation genes can alter the cell formation with an increase in estrogen. – artificially created with implantation of

sperm into a mice egg.

• DNA of the gamete will be sequenced. • DNA of the mice will go through mutation where BRCA1

and BRCA2 genes will be added to “X” sex chromosome.

• Egg will be fertilized• The fertilized egg will be implanted in to a female

mouse to go through a normal birth. • Over the life cycle of the mice the infected mice will be given

periodic dosage of estrogen everyday at 24 hour interval will be given after birth to observed when normal cell growth turns into cancer growth.

• As the estrogen level increases it will be easier to monitor when tumors arise. – Biopsy will be done every 24 hours to monitor cancer cell growth.

• According to research done before the proportion of cancer cells mutiplying varies from tumor to tumor. – If more than 6% to 10% of the cells are making new

cells, the rate of growth is considered unfavorably high.

– Test such as called S-phase fraction and Ki-67 tests should be performed to measure rate of cell growth.

• Once the amount of estrogen is identified for breast cancer formation, the same procedures were repeated at least five times to get consistent results.

Assessment

• Repeat Experiment at least 5 times• Analyze• The purpose was to test the effects of

estrogen on breast cancer. – If the mice developed breast cancer solely

based on the increase of estrogen in the body then this experiment will be considered a success.

– If at least 3 of the 5 experiments showed success then estrogen can be considered a major factor in breast cancer formation.

– It is important to analyze at what point in time cancer cell growth occurs.

– But if after years of periodic estrogen treatments given to mice shows no signs of cancerous cell growth then it will be certain that estrogen is not enough to activate the mutated targeted genes.

Next Steps

• If the experiment turns into success then the procedures can be tried on species on Chimpanzees

• If success if found there then we can work on formulating anti-estrogen hormones that will inhibit cancer cell formation by blocking the effects on estrogen on BRCA1 and BRCA2 mutated genes.

Questions?