Question

Given below are two statements, one is labeled as Assertion (A) and other one labelled as Reason (R).
Assertion (A) : Production of hypoxia-inducible transcription factor (HIF-1) produced in most carcinogenic tumor cell stimulates the production of glycolytic enzymes and glucose transporters (GLUT-1 and GLUT-3) to meetup their energy requirement.
Reason (R) : Most of the tumor cells grow in hypoxic condition.
In light of the above statements, choose the correct answer from the options given below.

• A. Both (A) and (R) are true and (R) is the correct explanation of (A).
• B. Both (A) and (R) are true but (R) is NOT the correct explanation of (A).
• C. (A) is true but (R) is false.
• D. (A) is false but (R) is true.

Hint:

HIF-1 acts as a metabolic master switch in cancer cells.
Under normoxic conditions, HIF-1$\alpha$ is continuously hydroxylated and degraded by the proteasome, whereas under hypoxic conditions, it is stabilized to drive anaerobic metabolism.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Solid tumors often grow rapidly, and as their mass increases, they outgrow the existing network of local blood vessels.
This leads to localized oxygen deprivation within the tumor, a condition known as hypoxia.
Carcinogenic cells adapt to this hypoxic microenvironment by altering their gene expression to switch from oxidative phosphorylation to anaerobic glycolysis (the Warburg effect).
Detailed Explanation:
- Evaluating Reason (R): Because solid tumors expand faster than new blood vessels can form (angiogenesis), the center of the tumor experiences low oxygen levels.
Thus, most tumor cells grow under hypoxic conditions, making Reason (R) true.
- Evaluating Assertion (A): In response to hypoxia, tumor cells stabilize the transcription factor Hypoxia-Inducible Factor 1 (HIF-1).
HIF-1 binds to specific response elements on the DNA to upregulate the expression of genes encoding glycolytic enzymes (such as hexokinase, phosphofructokinase) and high-affinity glucose transporters (GLUT1 and GLUT3).
This allows the tumor cells to import more glucose and accelerate glycolysis to meet their ATP requirements anaerobically.
Thus, Assertion (A) is true.
- Connecting A and R: Because the tumor cells reside in a hypoxic environment, they must upregulate HIF-1 to induce the metabolic changes necessary for survival.
Therefore, (R) is the direct physiological explanation for (A).

Step 2: Final Answer:
Both (A) and (R) are true, and (R) is the correct explanation of (A).