Role of Vitamin D receptor gene in radiation-induced neoplastic transformation of human breast epithelial cell.
1 Alpha,25-(OH)(2)-Vitamin D(3), the physiologically active metabolite of Vitamin D is known for its pro-differentiating and antiproliferative activity on various cancer cell lines. It exerts its growth-regulatory effects through binding to the Vitamin D recepter (VDR), a member of the steroid/thyroid/retinoic acid receptor family, which functions as a ligand-dependent transcription factor. There is accumulating evidence that Vitamin D may be an important determinant of both the occurrence and progression of breast cancer. Since radiation is an important etiological factor for breast cancer progression, it is important to study the role of VDR gene in radiation-induced breast carcinogenesis. This study is focused on a human breast tumor model developed by irradiating the spontaneously immortalized MCF-10F cell line with graded doses of high-linear energy transfer (LET) radiation followed by treatment with estrogen. Study of VDR gene by restriction digestion with ApaI, BsmI and TaqI detected no polymorphism but direct sequencing analyses identified few single-base mutations within intron 8 and exon 9 of the gene. Over-expression of the VDR gene was noticed in irradiated and tumorigenic cell lines compared with control. Likewise, immunohistochemical data indicated a significant increase in VDR intensity in irradiated and tumorigenic cell lines. Considering all these evidence, it is likely that VDR can be used as a prognostic marker of tumor progression in radiation- and estrogen-induced breast carcinogenesis.
Roy
Debasish
D
Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. droy@bnl.gov
Calaf
Gloria
G
Hei
Tom K
TK
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000235:genetics* / Q000528:radiation effects; D004252:DNA Mutational Analysis; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000032:analysis / Q000235:genetics*
D014408:Biomarkers, Tumor; D004967:Estrogens; D009363:Neoplasm Proteins; D018167:Receptors, Calcitriol