Intermediate Molecular Biomarkers for the Protective Effect of Pregnancy Against Breast Cancer
Annual summary rept. 15 Apr 2000-14 Apr 2003
BAYLOR COLL OF MEDICINE HOUSTON TX
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Epidemiological studies have consistently shown an early fill I-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization SSH to identify genes that are persistently up-regulated in the glands of estrogen and progesterone-treated Wistar-Furth rats 28 days subsequent to steroid hormone treatment compared to age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to prior treatment with estrogen and progesterone were identified. Two markers have been characterized in greater detail - RbAp46, and a novel gene currently designated GB7. Both genes were persistently up-regulated in the lobules of the regressed gland and required prior treatment with both estrogen and progesterone for maximal persistent expression. Sequence analysis and expression studies suggest that GB7 is a novel, non-coding RNA recent studies have shown that non-coding RNAs are an important class of regulatory molecules that may contribute to gene regulation through their association with chromatin remodeling, histone acetylationdeacetylation and transcription factor complexes as well as by RNA interference and by otherwise acting as inhibitory RNAs. RbAp46 has been implicated in a number of complexes involving chromatin remodeling - thus suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate, leading to protection against breast cancer.
- Medicine and Medical Research