Vitamin D Metabolism Is Deregulated During Breast Cancer Development
Posted Sep 17 2010 7:18am
As I have mentioned in several previous blog posts, getting enough vitamin D appears to be important for reducing breast cancer risk . The benefit of vitamin D in the fight against breast cancer has been reported to be due to the ability of vitamin D to modulate cell growth, cell death, and invasion. However, the regulation of vitamin D metabolism in breast tissues, particularly during breast cancer development are less clear.
Vitamin D metabolism and action is generally regulated through the vitamin D receptor and two enzymes, CYP27B1 and CYP24A1. The first of these enzymes, CYP27B1, is responsible for the synthesis of active vitamin D, while the second of these enzymes, CYP24A1, is involved in the breakdown of vitamin D. Therefore, the level and activity of these two enzymes help determine the amount of vitamin D available to bind to vitamin D receptors. A new breast cancer research study ( free to download ) has explored the relationship between these factors in normal, benign, and malignant breast tissue samples. For this breast cancer research study, investigators analyzed the presence of the vitamin D receptor and the two vitamin D metabolic enzymes in 29 normal breast tissues samples, 379 samples from benign breast lesions, 189 samples from in situ breast cancers, and 350 samples from invasive breast cancers. The breast cancer researchers reported
The vitamin D receptor was present at high levels in normal breast tissue samples (100%) and in benign lesions (~94%); however, vitamin D receptor levels were reduced in tissues from in situ breast cancer (47%) and invasive breast cancer (56%) samples.
The enzyme responsible for the production of active vitamin D, CYP27B1, was present in generally stable levels (64% of normal breast tissue samples, 56% of benign lesion samples, and 66% of in situ breast cancer samples); however, expression of this enzyme was reduced to 45% of invasive breast cancer samples.
CYP24A1, the enzyme responsible for the breakdown of vitamin D, is present in a greater percent of breast cancer samples. The expression levels of this enzyme were low in normal (30%) and benign (19%) breast tissue samples, but increased in invasive and in situ breast cancers (54-56%).
This is an important breast cancer research study showing us how vitamin D metabolism is altered during breast cancer development. According to the results of this study, normal breast tissues and benign lesions have high levels of vitamin D receptors, relatively high levels of the enzyme responsible for the synthesis of active vitamin D, and low levels of the enzyme responsible for vitamin D breakdown. This translates to a higher level of vitamin D available to bind to a high level of receptors and exert possible protective effects. In contrast, breast cancer tissues show lower levels of the vitamin D receptor, lower levels of the vitamin D synthesis enzyme, and higher levels of the vitamin D breakdown enzyme. This profile in breast cancer tissues translates to a lower level of vitamin D and a reduced ability to exert protective effects. This deregulation of vitamin D metabolism towards lower vitamin D availability and action appears to favor breast cancer development. Finding ways to re-balance vitamin D metabolism or prevent the deregulation of vitamin D metabolism during the early stages of breast cancer might become an important part of future breast cancer therapy.