PRAD1 (previously D11S287) is a putative proto-oncogene at 11q13, activated by overexpression through gene rearrangement or gene amplification in several types of human tumors including parathyroid adenomas, centrocytic lymphomas and other B-cell tumors with t(11;14), and breast cancers.
We have previously identified two genes (EMS1 and PRAD1/cyclin D1) in the chromosome 11q13 region that are frequently coamplified and overexpressed in human breast cancer and in squamous cell carcinomas of the head and neck (E. Schuuring, E. Verhoeven, W.J.Mooi, and R.J.A.M.Michalides, Oncogene 7:355-361, 1992).
These data implicate dysregulated expression of several cyclin genes, particularly cyclin D1, as a potential factor in the pathogenesis of breast cancer.
These results suggest that the frequency of overexpression is much higher than previously concluded from DNA-based analyses and that more than one-third of human breast cancers may contain excessive levels of cyclin D1.
These alterations in the cyclin D1 gene and mRNA suggest that altered expression of cyclin D1 may be important in the malignant transformation of this cell line, and support the identification of cyclin D1 as a dominant oncogene at 11q13 in human breast cancer.
We conclude that overexpression of cyclin D1 deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin D1 indeed plays an important oncogenic role in breast cancer.
In spite of the accumulating genetic evidence, however, there are no data regarding abundance and properties of the cyclin D1 protein in breast cancer.
Four antibodies were reactive with both PRAD1 fusion products and cell lysates of B-cell tumor cell lines with t(11;14)(q13;q32) and a breast cancer cell line with 11q13 amplification, on immunoblotting.
Cyclin D1 (PRAD1) protein expression in breast cancer: approximately one-third of infiltrating mammary carcinomas show overexpression of the cyclin D1 oncogene.
Using single-strand conformational polymorphism (SSCP) analysis, we have examined the coding region of the PRAD1 gene in 30 primary breast cancers and 25 parathyroid adenomas.
After a median follow-up period of 66 months, CCND1 or INT-2 amplification was not associated with significant increases in relapse or death from breast cancer.
Elevated levels of expression of cyclin D1 protein have been found in a variety of cancers, including breast cancer, head and neck cancer, non-small-cell lung cancer, and mantle cell lymphomas.
Cyclin D1 is necessary, rate-limiting and sufficient for G1 progression in breast cancer cells and regulation of cyclin D1 expression or function is an early response to steroid and steroid antagonist regulation of proliferation.