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Association of Rat p15^INK4B/p16^INK4 Deletions with Monosomy 5 in Kidney Epithelial Cell Lines but not Primary Renal Tumors¹

University of Texas M. D. Anderson Cancer Center, Smithville, Texas 78957 [D. F. K., D. T., C. L. W.], and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 [M. S., D. B.]

Recently the putative tumor suppressor gene p16^INK4 was mapped to human chromosome 9p21, which is homologous to rat chromosome 5. Monosomy of rat chromosome 5 occurs with high frequency in rat kidney tumor-derived cell lines (ERC lines). Thus, we studied these lines in order to investigate the involvement of p15^INK4B and p16^INK4 in the genesis of this tumor type. p15^INK4B and p16^INK4 were found by Southern blot analysis to be codeleted in five of seven of these lines. This was confirmed by Northern blot analysis with a probe for the rat p15^INK4B gene. In normal rat tissues, expression of p15^INK4B was abundant in lung (2.5 and 2.0 kilobases), less abundant in testis (2.5, 2.0, 1.1, and 0.9 kilobases), barely detectable in liver (2.0 kilobases), and not detectable in neonatal kidney, adult kidney, brain, heart, or spleen. In the ERC lines, p15^INK4B was expressed as a single 2.0-kilobase transcript observed only in those cell lines in which the gene was detected by Southern blot analysis. However, neither p15^INK4B nor p16^INK4 were deleted in 12 of 12 primary kidney tumors examined, suggesting that deletion of these genes is not directly involved in the process of renal tumor development but may be related to tumor progression or autonomous growth in vitro. A panel of rat kidney epithelial cell lines chemically transformed in vitro (TRKE lines) that had high-frequency monosomy 5 were also examined, but deletion of p15^INK4B and p16^INK4 was observed in only one of six of the TRKE lines. To our knowledge, this is the first reported investigation of these genes in rodent tumors and cell lines, and its data support the theory that alterations of genes located in the INF region of rat chromosome 5 may play a role in rodent cell transformation.

¹ This work was supported by National Cancer Institute/NIH Grant CA63613.

² To whom requests for reprints should be addressed, at University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Park Road 1C, Smithville, TX 78957.

Received 1/30/95. Accepted 3/ 3/95.

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