Scott Breast Cancer

Question 1

What are the two epithelial layers of the breast?

Answer 1

Luminal and myoepithelium

Question 2

What epithelial layer in the breast has progenitor cells?

Answer 2

Luminal

Question 3

What epithelial layer in the breast is ER alpha negative?

Answer 3

Myoepithelial layer

Question 4

What epithelium in the breast is ER alpha positive?

Answer 4

Luminal layer

Question 5

What epithelial layer in the breast contains stem cells?

Answer 5

Myoepithelial cells

Question 6

What is the inheritance pattern of BRCA mutations?

Answer 6

Autosomal dominant

Question 7

Why does inactivation of BRCA1 or BRCA2 result in breast cancer susceptibility?

Answer 7

BRCA1/2 are essential components of homologous recombination arm of DNA repair machinery

Question 8

What does homologous recombination repair in the DNA?

Answer 8

Ds DNA breaks

Question 9

A repair defect in BRCA1/2 mutant cells results in what?

Answer 9

Genomic instability

Question 10

Genomic instability creates the opportunity for what?

Answer 10

accumulation of somatic cancer causing mutations

Question 11

In the absence of BRCA1, what cells accumulate?

Answer 11

Progenitor cells

Question 12

What other genes in the DNA damage repair pathway contribute to familial breast cancers?

Answer 12

PALB2, CHECK2, ATM

Question 13

What is microevolution?

Answer 13

Random somatic mutations that result in dysregulated proliferation and inappropriate survival are selected for

Question 14

What type of genetic change is the driving force in development of both familial and sporadic cancers?

Answer 14

Somatic genetic changes

Question 15

Estrogen binding to ER alpha promotes transcription of what in normal breast tissue?

Answer 15

Amphiregulin, a secreted growth factor

Question 16

What causes the transcription of amphiregulin?

Answer 16

ER binding ER alpha

Question 17

What is the effect of amphiregulin?

Answer 17

Acts on nearby cells to promote proliferation

Question 18

In the breast, there are cells that express ER and cells that don’t… which cells proliferate?

Answer 18

The cells without ER

Question 19

In tumor cells expressing ER, what effect does estrogen have when binding?

Answer 19

Estrogen promotes transcription of cell cycle regulators like cyclin D1; the cells expressing ER undergo proliferation

Question 20

How are tumor cells different than normal breast epithelial cells?

Answer 20

Tumor cells have increased expression of ER and change what genes are regulated (ie increase Cyclin D1 vs amphiregulin)

Question 21

Breast tumor cells and normal cells are similar in what way?

Answer 21

No mutations or amplifications of genes encoding estrogen or ER

Question 22

How does ER promote transcription of a different set of genes in breast cancer?

Answer 22

Overexpression of the pioneer transcription factor FOXA1

Question 23

What is FOXA1?

Answer 23

Binds closed chromatin and increases cyclin D1 transcription

Question 24

Cyclin D1 is a key regulator in the what transition of the cell cycle?

Answer 24

G1/S transition

Question 25

What is the MOA of tamoxifen?

Answer 25

Estrogen analog that bind ER; tamoxifen-ER complex bind DNA and INHIBIT transcription (favors interaction with co-repressors not co-activators)

Question 26

ERBB2 is part of what receptor family?

Answer 26

EGF - tyrosine kinase

Question 27

Why is overexpression of ERBB2 oncogenic?

Answer 27

Does not require ligand binding for activation

Question 28

What drug blocks activity of ERBB2 homodimers?

Answer 28

Trastuzumab

Question 29

What durg blocks EGFR-ERBB2 heterodimers?

Answer 29

Lapatinib - binds and blocks kinase at active site