Material and Methods

Mutation analysis was performed by denaturating gradient gel electrophoresis and PCR described by Guldberg, et al. (17). Plasmids and Mutagenesis. Human wt PTEN DNA, kindly provided by Dr. Steck (University of Texas, Houston), was subcloned into the pxmyc vector according to Lukas, et al. (18). PTENpxmyc mutagenesis was performed as previously described (19). Cell Culture and Transfection. The human androgen insensitive prostate cancer cell lines DU-145 and PC-3 were...

Acknowledgement

These studies were supported by NIH Grant CA 66541. References 1. Bresciani F (1968) Topography of DNA synthesis in the mammary gland of the C3H mouse and its control by ovarian hormones an autoradiographic study. Cell Tissue Kinetics 1 51. 2. Ferguson DJ, Anderson TJ (1981) Morphological evaluation of cell turnover in relation to the menstrual cycle in the resting human breast. Br J Cancer 44 177-181. 3. Going JJ, Anderson TJ, Battersby S, et al (1988) Proliferative and secretory activity in...

References

Graham JD, Clarke CL (1997) Physiological action of progesterone in target tissues. Endocr Rev 18 502-519. 2. King RJB (1993) Estrogen and progestin effects in human breast carcinogenesis. Breast Cancer Res Treat 27 3-15. 3. Plu-Bureau G, Le MG, Sitruk-Ware R, et al (1994) Progestogen use and decreased risk of breast cancer in a cohort study of premenopausal women with benign breast disease. Br J Cancer 70 270-277. 4. Writing Group for the Women's Health Initiative Investigators (2002) Risks...

Deregulation of the Centrosome Cycle in Cancer

G1 S and G2 M checkpoints enforce the orderly completion of cell cycle events, and when triggered, they inhibit the formation and or activation ofCdks and thereby induce cell cycle arrest (63,64). Cell cycle checkpoints operate through the action tumor suppressor proteins p53 and Rb, and their downstream activation target Cdk2. Interestingly both p53 and Cdk2 may also physically reside at the centrosome, albeit only transiently (65,66). The physical presence ofkey proteins involved in...

Materials and Methods

A total of 20 cancer cell lines were used in this study, including Breast cancer, MCF-7, MDA-MB468, T47D, BT-549, PM1. Colorectal cancer, Gp5d, LoVo, DLD1, LS513, HT29, JJPF-OJC4. Gastroesophageal adenocarcinoma, OE19. Pancreatic carcinoma, MBQ-OJC1. Small cell lung cancer, H146, DMS92, JCA-OJC3. Hepatocellular cancer, HepG2. Haematopoietic neoplasm, KG-1, K562, Jurkat. All cell lines were maintained in RPMI-1640 medium supplemented with fetal calf serum, L-glutamine, penicillin,...

The Antiestrogenic Activity of Progestins Good or Bad Significance

It is clear that progesterone is a natural anti-E, thus partially explaining its protective effect in endometrium. We showed this anti-estrogenic activity on BC in vitro, since R5020, a pure progestin, inhibited the E-induced growth of MCF7 cells 8 . However, proposals concerning mechanism ofthis anti-estrogenic activity have varied with time Induction of 17P-OH-steroid dehydrogenase 9 , increase of inactive E-sulfates 20 , down regulation ofthe ER, and inhibition of transcription of...

CMyc Deregulation in Cancer

Myc Deregulation

C-Myc overexpression is associated with neoplasms of different tissues, including breast 11,12 , neuroblastoma 13 , cervical carcinoma 14 , malignant melanoma 15 , prostate cancer 16 , osteogenic sarcoma 17 , and lymphoid cancer 6, 18, 19 reviewed in 20 . Thus, Myc protein overexpression is an important player in cellular transformation 21-25 . Figure 1. c-Myc-dependent locus-specific and karyotypic instability in neoplasia. Figure 1. c-Myc-dependent locus-specific and karyotypic instability in...

Controversies and Discrepancies Concerning Progestin Action on Mammary Glands

Progestin Pathway

There is a relatively high consensus among laboratories on the mitogenic effect of Es on the mammary gland, and coherence between in-vitro studies on cell lines, and in-vivo epidemiological data, even though the detailed mechanism is not yet fully understood. By contrast, the effects of progestins after menopause, i.e., whether good or bad, have been extensively debated according to the laboratory and country involved. This is mostly due to the fact that different progestins are being used and...

Id1 Activity and MAPK Signaling Pathway

Mapk Egr Pathway

Earlier, we have shown that expression of Id-1 may be associated with advanced stages of PCA 17 . This implicates that Id-1 may function as an oncogene. Our earlier studies further suggest that one of the oncogenic functions of Id-1 may be through inactivation ofpl61NK4a, leading to the dysfunction ofpl61NK4a Rb tumor suppressor pathway 18 . Recently, Id-1 has been shown to facilitate human fibroblasts escaping senescence through the Ras-Raf-MEK signaling pathway 19 . In addition, one of the...

Results

Regulation of the hZEB-1 Promoter by Sex Steroids. Approximately 1 kb of the human ZEB-1 5'-flanking region was cloned by us from human genomic DNA by PCR and subcloned into the pBlueTOPO vector Invitrogen . This construct was named pBlueZEB974. To test the responsiveness ofthis DNA region to A, transient transfections were carried out in the PC-3 AR prostate carcinoma cell line, and the cells were treated with 100 nM DHT for 24 h prior to harvesting for analysis of P-galactosidase expression....

Chromosomal Instability A New Paradigm for Estrogeninduced Oncogenesis

Li, Jeffrey Salisbury, and Sara Antonia Li Introduction Human sporadic breast cancer BC comprises gt 90 of all BC cases whereas familial BC is less than 10 1 . Despite its likely multifactorial origin, there is now pervasive evidence from epidemiological and animal studies, developed over the past several decades, that the causation of human sporadic BC primarily involves female sex hormones, particularly estrogens Es 1-8 . This view is consistent with long standing epidemiological...

Hormones Centrosomes and Genomic Instability in Mammary Carcinogenesis

Breast Cancer Carcinogenesis

Stenoien, and Thea Goepfert Introduction The centrosome, a cytoplasmic organelle acquired at fertilization via paternal inheritance, plays a vital role in cell division and in the maintenance of cell polarity throughout development. The importance of the centrosome in achieving proper orientation and segregation of duplicated chromosomes and assuring stability of the eukaryotic genome is well established. The centrosome can be recognized in the cytoplasm of most...

Cell Molecular Biology Breast Cancer

Bi-directional Regulation of Human Progesterone Receptors and the Mitogen Activated Protein Kinase Pathway in Breast Cancer Cell Models Emily Faivre, Ming Qiu, and Carol A. 381 Abnormal Properties of Mutants in the Hinge Region of ErV Implications in Breast Cancer Carlos Mart nez-Campa, Pedro Zuazua, Juana Mar a Garc a-Pedrero, Pedro Casado, Pedro S nchez Lazo, and Sof a Ramos 391 The Effects of Eicosapentaenoic Acid Upon Proliferation and 17 -Dehydrogenase Activity in MCF-7 Breast Carcinoma...

Haojie Huang and Donald J Tindall Introduction

Surgical or pharmaceutical ablation of testicular androgens has been the most effective treatment of metastatic prostate cancer PCA since 1941 1 . Both normal and malignant epithelial cells ofthe prostate undergo programmed cell death apoptosis in the absence of androgens 2, 3 . However, a majority of PCA patients usually relapse with tumors becoming refractory to androgen ablation therapy, suggesting that relapsed cells are able to resist androgen withdrawal-induced cell death 4 ....

Comparisons of Parous and Hormone Protected Rats Similar or Different

Parous rats are susceptible to carcinogen-induced initiation and develop a high incidence of latent mammary cancers. However, these rats are protected from promotion and develop a very low incidence of overt mammary cancers. We determine whether the phenotypes of rats receiving protective hormone treatment mimic the protective effect of parous rats. That is, whether or not protective hormone treatments result in phenotypes susceptible to carcinogen-induced initiation, and develop latent mammary...

Characteristics of ILC Compared to IDC

Pathologic, Immunohistochemical and Genetic Characteristics. Classic ILC was first identified and distinguished from other types of BC by the pathologists Foote and Stewart in 1941. Based on their histopathologic descriptions, classic ILC is characterized by slender linear strands of cancer cells in single file, which are present diffusely throughout the tissue 4 . Lobular tumor cells are also typically small and uniform in size, and often have a signet-ring shape. Alternatively, IDC has a more...

The History of cMyc

C-Myc is the cellular counterpart ofthe viral oncogene v-myc that was identified as the transforming factor in avian retroviruses, MH-2, MC29 2 , CMII and OK 10 3 . Subsequently, it was discovered that bursal B-cell lymphomas in retrovirus-infected fowl were caused by retroviral integrations in or near the c-myc proto-oncogene, which caused constitutive expression of c-myc. In some cases, these transcripts originated at the promoter in the long terminal repeat LTR of the retrovirus 4 . In other...

Participants

Marcelo Aldaz The University of Texas, M.D. Anderson Cancer Center, Smithville, TX, USA Lorenzo Alonso Hospital Universitario de M laga, Madrid, SPAIN Leoncio Arribas Alpuente Hospital Universitario de M laga, Madrid, SPAIN Bynthia Maria Anose Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA Manuel Valladares Ayerbes Medical Oncology, Pathology and Research Units, Medicine Department, Juan Canalejo University Hospital, La Coru a,...