This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hundley, J. E. Articles by Windle, J. J. Search for Related Content PubMed Articles by Hundley, J. E. Articles by Windle, J. J.

Differential Regulation of Cell Cycle Characteristics and Apoptosis in MMTV-myc and MMTV-ras Mouse Mammary Tumors¹

Departments of Cellular and Structural Biology [J. E. H.], Pathology [D. A. T.], and Medicine/Oncology [S. G. H.], The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284, and Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, Texas 78229 [J. J. W., S. K. K.]

We have used the MMTV-myc and MMTV-ras transgenic mouse mammary tumor models (T. A. Stewart et al., Cell, 38: 627–637, 1984, and E. Sinn et al., Cell, 49: 465–475, 1987) to evaluate how the c-myc and v-Ha-ras oncogenes influence tumor growth characteristics in vivo. MMTV-myc tumors had much higher levels of spontaneous apoptosis than MMTV-ras tumors, whereas intermediate levels were observed in MMTV-myc/ras tumors. Significant differences in cell cycle characteristics were also observed in tumors from mice of the three genotypes. Tumors from MMTV-myc mice had lower G₁ and higher S-phase fractions than MMTV-ras tumors, with intermediate values again observed in the MMTV-myc/ras tumors. Despite these differences, however, tumor growth rates for the different groups were similar. These findings high-light the importance of the balance between cell cycle regulation and cell death in determining the kinetics of tumor growth and indicate that distinct oncogenes can have a profound influence on that balance.

¹ This study was supported by a developmental project subgrant (to J. J. W.) from NIH grant P50 CA58183, American Cancer Society grant DHP-150 (to J. J. W.), and the San Antonio Cancer Institute Cancer Center Support Grant P30 CA54174.

² Present address: Coulter Corporation, 11800 Southwest 147th Avenue, Miami, FL 33196.

³ Present address: Texas Oncology, P. A., 7940 Floyd Curl Drive, Medical Center Tower II, Suite 720, San Antonio, TX 78229.

⁴ To whom requests for reprints should be addressed, at Institute for Drug Development Cancer Therapy and Research Center, 8122 Datapoint Drive, Suite 700, San Antonio, TX 78229.

Received 11/14/96. Accepted 12/23/96.

This article has been cited by other articles:

				S.-Q. Kuang, L. Liao, H. Zhang, A. V. Lee, B. W. O'Malley, and J. Xu AIB1/SRC-3 Deficiency Affects Insulin-Like Growth Factor I Signaling Pathway and Suppresses v-Ha-ras-induced Breast Cancer Initiation and Progression in Mice Cancer Res., March 1, 2004; 64(5): 1875 - 1885. [Abstract] [Full Text] [PDF]

				T. Petit, D. J. Bearss, D. A. Troyer, R. M. Munoz, and J. J. Windle p53-independent Response to Cisplatin and Oxaliplatin in MMTV-ras Mouse Salivary Tumors Mol. Cancer Ther., February 1, 2003; 2(2): 165 - 171. [Abstract] [Full Text] [PDF]

				E. L. Milliken, R. K. Ameduri, M. D. Landis, A. Behrooz, F. W. Abdul-Karim, and R. A. Keri Ovarian Hyperstimulation by LH Leads to Mammary Gland Hyperplasia and Cancer Predisposition in Transgenic Mice Endocrinology, September 1, 2002; 143(9): 3671 - 3680. [Abstract] [Full Text] [PDF]

				D. J. Bearss, R. J. Lee, D. A. Troyer, R. G. Pestell, and J. J. Windle Differential Effects of p21WAF1/CIP1 Deficiency on MMTV-ras and MMTV-myc Mammary Tumor Properties Cancer Res., April 1, 2002; 62(7): 2077 - 2084. [Abstract] [Full Text] [PDF]

				J. A. Engelman, R. J. Lee, A. Karnezis, D. J. Bearss, M. Webster, P. Siegel, W. J. Muller, J. J. Windle, R. G. Pestell, and M. P. Lisanti Reciprocal Regulation of Neu Tyrosine Kinase Activity and Caveolin-1 Protein Expression in Vitro and in Vivo. IMPLICATIONS FOR HUMAN BREAST CANCER J. Biol. Chem., August 7, 1998; 273(32): 20448 - 20455. [Abstract] [Full Text] [PDF]

				R. E. Barrington, M. A. Subler, E. Rands, C. A. Omer, P. J. Miller, J. E. Hundley, S. K. Koester, D. A. Troyer, D. J. Bearss, M. W. Conner, et al. A Farnesyltransferase Inhibitor Induces Tumor Regression in Transgenic Mice Harboring Multiple Oncogenic Mutations by Mediating Alterations in Both Cell Cycle Control and Apoptosis Mol. Cell. Biol., January 1, 1998; 18(1): 85 - 92. [Abstract] [Full Text]