© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 7, 467,
April 3, 2002
© 2002 Oxford University Press
IN THIS ISSUE |
Comparisons of the genes expressed in malignant cells with those expressed in normal cells of the same tissue may provide a means to identify candidate oncogenes and tumor suppressor genes. Jing et al. (p. 482) used several rounds of selective mRNA comparisons to identify mRNAs expressed specifically in benign normal prostate cells but not in malignant prostate cancer cells. The authors identified tazarotene-induced gene 1 (TIG1), a retinoic acid receptor-responsive gene, as a gene that was expressed in normal prostate and in benign prostatic hyperplastic tissues but in only four of 51 malignant prostate tissues. The authors cloned TIG1 and, after transfecting it into a highly malignant prostate cancer cell line, showed that both the in vitro invasiveness and in vivo tumorigenicity of the cell line were reduced. The authors conclude that TIG1 may be a tumor suppressor gene whose diminished expression may be involved in the malignant progression of prostate cancer.
In an editorial, Lotan (p. 469) discusses how and where TIG1 fits into the carcinogenesis process by focusing on the general characteristics of a tumor suppressor and by highlighting what is known about the expression and regulation of TIG1.
Hormone Replacement Therapy and Ovarian Cancer
Hormone replacement therapy (HRT) relieves symptoms related to menopause and may have other benefits, including preventing osteoporosis. However, it is unclear whether HRT—either with estrogen alone (ERT) or with estrogen plus progestins (added either sequentially [HRTsp] or continuously [HRTcp])—is associated with a change in the risk of epithelial ovarian cancer (EOC). Riman et al. (p. 497) carried out a nationwide case–control of 655 case patients with histologically verified incident EOC and 3899 randomly selected control women. Ever users of both ERT and HRTsp, but not HRTcp, had statistically significantly higher risks of EOC than never users. Risks were elevated for all subtypes of EOC, and the risk increases were greatest in women who had used hormones for more than 10 years. The authors advocate cautious interpretation of their results, noting that for women to make informed decisions about HRT they need to consider all the risks and benefits of different HRT regimens.
Race, Socioeconomic Status, and Breast Cancer Treatment
African-American women are more likely than white women to have late-stage breast cancer at diagnosis and to have less favorable outcomes. Breast cancer treatment also differs between African-American and white women. To determine whether these differences are more attributable to race or to socioeconomic status, Bradley et al. (p. 490) analyzed data from 5719 women diagnosed with breast cancer that they obtained from a population-based cancer registry linked to Medicaid claim files. They found that, after controlling for age, socioeconomic status, and insurance coverage, African-American women were not statistically significantly different from white women with respect to breast cancer stage at diagnosis and survival. However, African-American women were less likely to receive surgery than white women, but those who received surgery were more likely to have breast-conserving surgery than were white women. The authors conclude that low socioeconomic status is more strongly associated with unfavorable breast cancer outcomes than is race.
In an editorial, Brawley et al. (p. 471) discusses why distinguishing between the effects of race and poverty on breast cancer outcomes is important. He suggests that better definitions of socioeconomic factors that influence cancer etiology and behavior are needed, as are studies to determine why the poor receive less than adequate care and how the situation can be remedied.
Effects of Depsipeptide in Lung Cancer Cell Lines
Histone deacetylases (HDAC) regulate histone acetylation. HDAC inhibitors, such as depsipeptide FR901228 (FK228), induce apoptosis in cancer cells via mechanisms that presently are unclear. Yu et al. (p. 504) observed altered expression of cell-cycle related proteins, reduced expression of mutant p53 but not wild-type p53, and depletion of several signaling-related proteins in cultured lung cancer cells following FK228 exposure. The reduced expression of mutant p53 and signaling-related proteins was associated with an inhibition of binding to heat shock protein (Hsp) 90, a protein that promotes the stabilization of multiprotein complexes. Reduced interactions between Hsp90 and client oncoproteins coincided with acetylation of Hsp90. The authors conclude that FK228 has mechanisms of action other than inhibition of histone deacetylation that contribute to the potency of this novel antitumor agent.
Osteopontin: Marker of Colon Cancer Progression
New tumor markers and markers of tumor progression are needed for improved staging and for the better assessment of cancer treatments. Gene expression profiling techniques offer the opportunity to discover such markers. Agrawal et al. (p. 513) investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. Total RNA from 60 human colon tumors of multiple stages were pooled within stages, and compared with 10 pooled normal mucosal specimens by using oligonucleotide expression arrays. More than 300 new tumor markers were identified, 11 of which were validated by Northern analysis. The authors found that the gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. They conclude that the sample pooling approach can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile.
Cancer-Specific Expression of the Survivin Promoter
Survivin, an inhibitor of apoptosis, appears to be overexpressed in common cancers but not in corresponding normal adult tissues. Bao et al. (p. 522) investigated whether the promoter for the survivin gene controls cancer-specific gene expression. They found that survivin protein was detected in all cancer cell lines but not in most normal adult mouse tissues. After transfection, the survivin promoter was more active in cancer cell lines than in normal ovarian surface epithelial cells or mouse 3T3 cells. The authors conclude that the survivin promoter may be useful in controlling gene expression in cancer cells.
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