In a recent study by Elizabeth Snyderwine and colleagues, cDNA microarray profiling was used to compare the expression profiles for 6900 genes in normal and malignant breast tissues from rats. RNA was extracted from the following tissues:
a. Breast tissue from virgin rats
b. Breast tissue from pregnant rats
c. Breast tissue from lactating rats
d. Breast carcinoma induced by the meat-derived carcinogen PhIP
e. Breast carcinoma induced by the experimental carcinogen DMBA
After the microarray slides were hybridized with labeled cDNAs derived from these 5 populations of RNAs, the data were analyzed by several different comparisons.
In comparison 1, tissues a, b, and c were grouped together as “normal†tissue samples, and d and e were grouped as “carcinoma†samples. Genes that were either induced (more than twofold increase in expression) or repressed (more than twofold decrease in expression) in both carcinoma samples relative to all three normal samples were determined. A partial listing of differentially expressed genes is shown in the accompanying table.
Induced Genes Cell-Growth and Cell-Cycle-related Genes Platelet-derived growth factor A chain (PDGF-A) Cyclin-dependent kinase 4 (Cdk4) Cyclin D Signal-Transduction and Transcription-Related Genes STAT5a Repressed Genes Extracellular Matrix Genes Alpha 1 type V collagen Fibronectin 1 Desmin
A) What was the purpose of analyzing breast tissue from pregnant and lactating rats?
B) What characteristic of cancer is promoted by the overexpression of PDGF-A, Cdk4, and cyclin D?
C) What characteristic of cancer might be promoted by the repression of extracellular matrix genes?
D) STAT5a is a transcription factor that regulates the expression of cyclin D, Bcl-XL, and other genes. Why is it possible for these carcinomas that no mutation occurs in the cyclin D gene despite its overexpression?
E) How does overexpression of Bcl-XL lead to cancer?
F) On the basis of this information, what can be generalized about the molecular profile of breast carcinomas?
G) Would you anticipate greater or fewer differences in gene expression if two distinct types of cancer (e.g., breast carcinoma vs. B-cell lymphoma) induced by the same carcinogen were compared by microarray analysis?